[References]

The Peroxisomal Disorders

DISCLAIMER: The purpose of this page is to sketch, in a general and non-technical manner, the current state of knowledge on the nature and functions of the peroxisome, and the diseases resulting from peroxisomal dysfunction. This information is drawn from a range of medical literature, and is intended to reflect areas in which there is prevailing consensus of opinion. It is believed that the concepts and models discussed represent the best available, and most widely accepted, understanding of the subject.
    The author of this page has no medical background and the content is targeted toward a similar readership, typically the parents of affected children. I hope that it may also be of some benefit to health care workers who are not specialists in the field and other professionals working with these children.
    HOWEVER, it is hereby expressly stated that the following discussion is NOT to be considered medical advice, or as having any particular relevance to any particular case, or as representing all possible schools of thought.  In particular, the subjects of therapy and diet are not within its scope, except in passing mention.
IT'S REAL SIMPLE: If you need medical advice you need to be consulting with a physician. Go. Now. We'll still be here.

OVERVIEW
    The peroxisome is one of several types of organelles present in almost all eukaryotic cells (cells having a nucleus), both plant and animal, an organelle being a specialized structure within a cell where particular chemical and metabolic functions take place. Close metabolic interrelationships exist between the peroxisomes and the other organelles of the cell, the chemical result of one organelle's process often being the raw material of the next. The precise means by which these transports occur is not fully understood; it is surmised from the chemistry involved, but usually not accessible to direct observation. This is true for much of the understanding of the peroxisomes.
    A peroxisome is a round or oval body with an average diameter of 0.5 micron. A cell will contain not one, or even several, peroxisomes but possibly several hundred. The peroxisome is bound by a membrane composed of lipids and proteins, and its interior (called the matrix) is made up of various proteins which function as enzymes in metabolic processes.
    Peroxisomes are especially abundant, and larger in size, in the cells that make up the liver and kidneys of humans and other mammals.  Although all peroxisomes are biochemically active, those in liver and kidney perform the majority of peroxisomal function. In a developing fetus and (in humans) for a few weeks after birth, peroxisomes are also abundant in the oligodendrocytes, the cells which surround the developing central nervous system, act to guide its growth, and synthesize the myelin sheath which insulates it.
    The peroxisome was "discovered" in 1954 by a doctor named Rhodin, and over the next ten years some of its more basic functions were determined.  This was in large part the work of another doctor named de Duve. The name peroxisome derives from the early observation of the role of this organelle in cellular respiration, a process involving both the generation and decomposition of hydrogen peroxide. Catalase, the enzyme which breaks down hydrogen peroxide, is the necessary identifying marker of the peroxisome: by definition, a peroxisome must contain it and a subcellular structure not containing catalase is not considered a peroxisome.
    It is now known that approximately fifty different biochemical reactions occur entirely or partially within the peroxisome. Some of the processes are anabolic, meaning constructive, and lead to the synthesis of essential biochemicals: bile acids, cholesterol, ether-phospholipids (plasmologens), and docosahexaenoic acid. Some of the processes are catabolic, meaning destructive, and lead to the decomposition of certain fatty acids, particularly very long chain fatty acids (VLCFAs) and others such as phytanic acid, pipecolic acid, and the prostaglandins.  Most of these processes involve coordinated interactions between the peroxisomes and other organelles, and each metabolic step is dependent upon the successful completion of the previous. For example, the decomposition of the VCLFAs and phytanic acid is a process shared by the peroxisomes and the mitochondria, the correct functioning of the peroxisomal steps being essential to the overall success of the process. Likewise, the final steps in the synthesis of the plasmologens occur in the endoplasmic reticulum, but the process depends on precursors which are synthesized in the peroxisomes.

PEROXISOMAL BIOGENESIS
     A peroxisome doesn't last very long. Its "life span" is just a day or two, so there has to be a constant process of replacement, the formation of new peroxisomes. This process, referred to as peroxisomal biogenesis or peroxisomal assembly, goes like this:
1)  The proteins which will make up the peroxisome's membrane and matrix are synthesized by free ribosomes, another type of organelle. The ribosome is the site at which messenger RNA, bringing genetic information from the DNA in the cell nucleus, is translated into the variety of proteins which make up the cell and its organelles. (Some organelles, notably the mitochondria, also contain their own DNA and ability to synthesize some proteins internally. This has led to the hypothesis that the mitochondria (and possibly also the peroxisomes, which however do not contain their own DNA) were originally independent life forms that have evolved into a complex symbiosis with their host, the cell. At any rate, the vast majority of the proteins necessary to the cell and its organelles are synthesized on the ribosomes from nuclear genetic coding.)
2)  The completed proteins enter the cytosol, which is (roughly speaking) that portion of the cell's interior that isn't either the nucleus or an organelle.
3)  From the cytosol, the peroxisomal membrane and matrix proteins are imported into pre-existing peroxisomes, which exist either singly or in a network called a peroxisomal reticulum. These expand with the upload of the new material and at a certain point new peroxisomes are formed either by division or budding from the reticulum.
    The various proteins are directed to their correct positions in the peroxisome - either incorporated into the membrane or passing  through it into the matrix - by means of peroxisomal targeting signals (PTSs). A PTS is a sequence of amino acids usually at or near an end of the protein, synthesized along with it on the ribosome. This sequence is not properly a part of the actual protein but is a tag essentially identifying it to a second protein known as a PTS receptor. A PTS receptor is a mobile protein which repeatedly shuttles between the cytsol - recognizing and binding the PTS protein - and the peroxisome, separating from it and leaving it for import.
     About half of the peroxisomal matrix proteins are identified by a sequence known as PTS1 (SKL, serine-lysine-leucine, or certain variants), and several more by a sequence known as PTS2, occuring at opposite ends of the protein. There are also proteins which have both the PTS1 and PTS2. Other known matrix proteins have neither the PTS1 nor the PTS2, so it is assumed that there must also be a PTS3 and possibly others, trickier to identify as they don't occur at the ends of the protein, but internally. The proteins which are components of the peroxisomal membrane (integral membrane proteins, IMP) also have a type of internal PTS.
     The receptors for PTS1 and PTS2 have been closely studied, both the functioning proteins and the genes which code for them. Their role in peroxisome biogenesis is well-understood, and there is known correlation between mutuations of these genes and some of the peroxisomal diseases, the biogenesis disorders.
     There are about fifteen other proteins known to be necessary to the correct assembly of a peroxisome. For the most part the genes which code for them have been identified, although the exact function of the protein may be only more or less understood. In addition to the PTS1 and PTS2 receptors (and presumably the PTS3 receptor not yet identified), there are proteins known as chaperones (heat shock proteins) which go along for the shuttle ride and somehow mediate between the PTS-protein and the PTS-receptor. Others known as gatekeepers are possibly involved in the separation of the protein from the receptor. There are integral membrane proteins which serve as the docking sites for the receptors and their cargos, and
also as the passageways by which the proteins enter the matrix. There are proteins which regulate the numbers of peroxisomes within a cell, and still others which regulate the distribution of peroxisomes at the time of cell division.
      Collectively, these proteins - the ones involved in peroxisome biogenesis, as distinct from the matrix enzyme proteins involved in peroxisomal function - are known as peroxins. These proteins, and the genes which code for them, are known by the acronym PEX and they are numbered PEX1, PEX2, &c. in the order of their original published descriptions. For instance, PEX5 is the gene which codes for the PTS1 receptor, and PEX7 is the gene which codes for the PTS2 receptor. By no means is the nuts and bolts operation of the targeting signals and the peroxins completely understood or agreed upon. Much of it is downright mysterious. But aside from a number of technical questions (as, for example, whether the receptors uncouple from their proteins at the peroxisome's surface or if this happens in the peroxisome's interior) which are under specialized and on-going investigation, the basic model of peroxisome assembly is pretty much accepted. Much of this knowledge has been gained by the study of certain yeasts. There is an almost complete genetic and chemical identity between peroxisome assembly in these yeasts and in humans, so that  understanding  the gene mutations in the yeast peroxins is directly applicable to understanding the human peroxisome biogenesis disorders.

PEROXISOMAL DISORDERS
    Depending on who's doing the counting, there are about 16 or 17 peroxisomal disorders currently known, with a few more suspected or under investigation. They are typically thought of as falling into one of three groups; peroxisome biogenesis disorders (PBDs), peroxisomal multi-enzyme disorders, and peroxisomal single-enzyme disorders. This is a biochemical classification; a patient's cells are cultured and observed for particular enzymatic activity, a patient's blood is analyzed for the presence or lack of particular biochemicals associated with known peroxisomal functions, and compared against a norm, these types of measurements help to indicate specific defects of peroxisomal function. Diagnosis is aided (but not fully determined) by this identification of specific biochemical defects.
    The biochemical classification has been customary since the early 1980s, when the peroxisomal disorders were first being recognized and described. It is the basis of most subsequent diagnosis and casework.  It does have its limitations, mainly in that the existence of a particular biochemical abnormality doesn't always correlate neatly with a particular patient or that patients with entirely different biochemical abnormalities may be clinically similar. As identification of the gene mutations which cause the peroxisomal disorders proceeds, it becomes possible that eventually they will all be classified genetically, rather than chemically.

Peroxisome Biogenesis Disorders (PBDs)
    These are also variously referred to as the peroxisome assembly disorders, the generalized peroxisomal disorders, or the peroxisomal polydystrophy syndromes.

Cerebro-hepatic-renal (Zellweger) syndrome (ZS) (ZWS1)
     ZWS1 [MIM No. 214100]
     ZWS2 [MIM No. 170995]
     ZWS3 [MIM No. 170993]
Neonatal adrenoleukodystrophy (NALD) [MIM No. 202370]
Infantile Refsum disease (IRD) [MIM No.266510]

    The peroxisome biogenesis disorders (PBDs) are diseases in which the entire process of peroxisomal assembly has malfunctioned, and nearly all normal peroxisomal functions are either absent or deficient. Sometimes, this means that the peroxisomes themselves fail to form, or fail to form in sufficient numbers; other times "ghost peroxisomes" form, having somewhat the appearance of the real thing, but lacking the matrix enzymes necessary to function.
    ZS, NALD, and IRD have so many features in common - biochemically, genetically, and clinically - that they are typically considered a single continuum of disease, with ZS being the most severe and IRD the least.  However, there are also some distinct differences between them. Each has characteristics which set it apart from the others, and the names are not used interchangably.
    Because they all involve the same generalized failure, the PBDs share a common set of biochemical abnormalities: the entire range of peroxisomal functions.  Of these, some half dozen or so seem to commonly come up as being particularly relevant to the disease states:
> impaired synthesis of ether-phospholipids (which are molecules that go into making up membranes, especially in the central nervous system, and in the formation of myelin);
> impaired synthesis of docosahexaenoic acid (DHA, a long chain fatty acid which is a component of certain more complex lipids, especially in the membranes of the central nervous system)
> impaired decomposition (oxidation) of very long chain fatty acids (VLCFAs),
    A fatty acid with more than 22 carbon atoms in its chain is called a VLCFA.  The peroxisome is involved, along with the mitochondria, in the process of shortening these molecules to a length that either the body can use or is able to rid itself of.  When they can't be broken down, they accumulate, especially in the central nervous system. While not toxic in the sense of being poisonous, the accumulation of VLCFAs is disruptive to the structure and stability of the affected cells, for reasons which are not completely understood.
> impaired oxidation of phytanic acid (an unusual fatty acid which also accumulates detrimentally when it isn't broken down)
    There are dozens of others, and the chemistry here is beyond the purpose of this page. For example, the peroxisomes are also involved in the metabolism of alcohol. It is really the complex of abnormalities that define the PBDs, and no single one should be thought of as isolated from the others. And to a large degree, there is uncertainty as to how exactly these abnormalities, or what combination of them, cause the pathology and disability of the PBDs.

   A child with Zellweger syndrome (ZS) has dysmorphic facial features (with high forehead and flat nose bridge, wide-set eyes and low-set ears), and deformed limbs and joints, with calcium deposits in the cartilage. The liver and kidneys are usually diseased or abnormal.  There is a fundamental malformation of the brain in the developing fetus (abnormal neuronal migration), and myelination does not proceed completely (hypomyelination). There is usually retinal or other eye disease, and almost always sensorineural (cochlear) hearing loss. The child is hypotonic and prone to epileptic seizures. There is a profound lack of any normal psychomotor development. ZS is fatal early, usually within the first year of life.
   There are known to be at least three different gene defects which can cause ZS: ZWS1, ZWS2, and ZWS3 are the names given to these forms.  Only the specific genetic causes are different; outwardly these are all essentially the same.
   Neonatal adrenoleukodystrophy (NALD) has many characteristics in common with ZS, and some distinct differences. The dysmorphic facial features and skeletal abnormalities are less pronounced. There is no calcification of cartilage. There is liver disease, but not the kidney cysts associated with ZS. The adrenal glands are diseased.  The neuronal migration defect in the developing brain is not as extensive as in ZS, but there are severe abnormalities of myelination. There is retinal or other eye disease and also sensorineural hearing loss. These children are hypotonic and prone to seizures. Psychomotor development is profoundly affected.  NALD is fatal, usually within the first ten years.
   Unlike ZS and IRD, NALD is characterized by a process of active demyelination (deterioration of the existing myelin sheath) and by disease of the adrenal glands. When it was first described, in 1978, it took its name from these two similarities with X-linked adrenoleukodystrophy, being considered a "neonatal" form of it. This was at a time before there was even a concept, let alone systematic classification and study, of the peroxisomal disorders. The actual relation between NALD and ALD was unknown, and the similarity of NALD to ZS was not appreciated.
    Infantile Refsum disease (IRD) has characteristics in common with both ZS and NALD, but relative to them the pathology and abnormalities of IRD are not as devastating. This shouldn't be overstated. A child with IRD is still very sick and has severe physical, sensory, and developmental disabilities. However, with time and patience, IRD children usually attain to some degree of motor, cognitive, and communication skills.
    A child with IRD has dysmorphic facial features, often of great subtlety and not recognized unless pointed out. He is apt to be small for his age, but body and limbs are correctly proportioned. The liver is typically enlarged, and there may be some amount of dysfunction. The adrenal glands are possibly affected. The neuronal migration defect, similar to that of NALD, is not as extensive as in ZS. Myelination is abnormal, but there is no active demyelination. There is almost always retinal or other eye disease, and generally sensorineural hearing loss.  In IRD, the child is usually born hearing and the loss occurs sometime between six months and a year of age. A child with IRD is probably going to be hypotonic, though not always severely. IRD is sometimes associated with seizure disorders, but not typically. Psychomotor development is severely affected, but is by no means arrested. IRD is also fatal, but survival into the teens and twenties and even beyond is known.
    In some cases, infants with IRD will undergo spontaneous bleeding episodes, in particular intercranial hemorrhage. This may be due to a liver dysfunction that interferes with the synthesis of vitamin K. If the child survives this, the resulting brain injury is an unknown and complicating factor in his development. Its effects, if any, can hardly be distinguished against the backdrop of the IRD. The brain injury may possibly result in a seizure disorder which otherwise would have been absent.
   IRD was originally called infantile phytanic acid storage disease, the first described cases (1982) noting this specific biochemical abnormality.  Since the one disease at that time known to be associated with abnormal levels of phytanic acid was Refsum disease, these cases were considered to be an "infantile" form of it. The similarities of the two were noted (especially in the eye disease), but the number of differences between them were striking, and IRD and Refsum disease were always understood to be two separate entities. As with NALD, this was at a time when there was no study or classification of peroxisomal disorders. Within a couple of years the true position of IRD in relation to ZS and NALD, and in relation to Refsum disease, was pretty much established. But as with NALD, the name stuck.
   NALD and IRD are names that sometimes can lead to confusion, historical curiousities that don't reflect their true identities. On the other hand, there are sufficient distinctions between ZS, NALD and IRD to warrant having three names, and these are as good as any. Probably they're with us for a while.
   Accepting these distinctions, there is still a great deal of overlap between ZS, NALD, and IRD. An abnormality typical to one may show up in another, or itself be absent. It is a continuous and dynamic spectrum, from the most profoundly involved child with ZS to a teenager with IRD who bowls in Special Olympics. Since the common defect of the PBDs is known, it seems logical to speculate that the spectrum of disease is reflective of a corresponding spectrum of peroxisome biogenesis failure, that in the most severe cases of ZS the failure is nearly complete and that in IRD some manage to form and carry on (thought to possibly be what's going on with the ghost peroxisomes), or in some other way peroxisomal functions are partially carried out. There is some evidence for this being the case, and it does seem a natural way of understanding it. Beyond this there is as yet no resolved picture. The actual steps from defective genes to defective peroxisomes, from abnormal biochemistry to the disease states, are not fully understood.
    Hyperpipecolic acidemia [MIM No. 239400] was another disease described before there was a study of peroxisomal disorders, and was named for the observed high levels of pipecolic acid in the patients. This was a name that didn't stick. The described cases are thought to be indistinguishable from either NALD or IRD, and the term hyperpipecolic acidemia was eventually considered unnecessary.
     There is at least one described case referred to as pseudo-IRD. This was considered to be a PBD, as catalase-containing peroxisomes did not exist. There were, however, peroxisome-like structures which did contain some peroxisomal matrix proteins, and in which some processes did continue almost normally.

   The peroxisome biogenesis disorders are autosomal recessive. They occur in all countries and among all races and ethnic groups. They are diseases of extreme rarity, but any discussion of just how rare immediately falters.  Estimates of birth frequencies vary from 1:30,000 to 1:150,000, but the level of conjecture is high. Consistent and reliable census data is itself the rarity.
    There is no cure. In general, what therapies do exist are dietary: for example, attempting to limit the intake of VLCFAs and/or phytanic acid, or supplementing the diet with DHA or anti-oxidant vitamins. The theory here is that the pathology and disabilities of these diseases are caused by the biochemical abnormalities (even without always understanding just how) and that therefore they can possibly be alleviated by artificially correcting those abnormalities. This is a reasonable line of thought, and dietary therapies of various kinds are widely practiced. On the other hand, some doctors hold that since the peroxisome dysfunction is global and involves so many different abnormalities (in relations that aren't even fully known) the overall complex is beyond this sort of correction.  Consistent, controlled, long-term studies of the effects of dietary limitation and/or supplementation are non-existent. Nor would there be any medical consensus on what that diet should be anyway. Commonly, seizure disorders are treated with anti-convulsants, and IRD children with the bleeding disorder take vitamin K to control it.

Peroxisomal Multi-Enzyme Disorders

    These are diseases in which several of the proteins necessary to peroxisomal function are lacking, but there is not a global loss of function as in the PBDs. Because it contains catalase, the peroxisome itself is considered intact, and not the result of a general assembly failure.
    However, this classification is not universally used and sometimes these diseases are counted among the PBDs (i.e., resulting from mutation of peroxin genes). Considered this way, the peroxisome biogenesis disorders fall into four groups (and include RCDP):
- failure or deficiency in import of PTS1 only (ZS, NALD)
- failure or deficiency in import of PTS2 only (RCDP)
- failure or deficiency in import of both PTS1 and PTS2 (ZS, NALD, IRD)
- failure or deficiency in the peroxins necessary to biogenesis of the peroxisomal membrane, also in the import of both PTS1
  and PTS2 (ZS, NALD, IRD)

Rhizomelic chondrodysplasia punctata (RCDP) [MIM No. 215100]
Zellweger-like syndrome

    RCDP involves defects of three or four specific enzymes in otherwise apparently intact and functioning peroxisomes. These dysfunctions result in the impaired synthesis of ether-phospholipids, the malformation of an enzyme necessary to liver function, and the impaired oxidation with subsequent accumulation of phytanic acid. RCDP is recognized by this particular set of abnormalities. Chondrodysplasia punctata is a broader term, including other disorders which are not peroxisomal, or not definitely determined to be (e.g. Conradi-Hunnermann syndrome). RCDP is the most severe of these; the term is reserved for the peroxisomal disorder.
    RCDP is characterized by certain skeletal abnormalities from which it derives its name, a dwarfism marked by a disproportionate shortening of the upper limbs (rhizomelia), and abnormalities in the formation of cartilage (chondrodysplasia punctata, specifically an abnormal calcification of cartilage). The child's head and face are dysmorphic, cataracts are typical but not other eye disease. Her psychomotor development is severely affected. Unlike the PBDs, RCDP is not associated with neuronal migration defects or with abnormalities of myelination. At its most severe, RCDP is fatal within the first year; however survival into the teens is known.
    To somewhat complicate the nomenclature there are also several described cases in which RCDP is not associated with rhizomelia. This non-rhizomelic (yet peroxisomal) CDP is genetically and biochemically identical to RCDP, and is understood to be a less severe form of it, not a separate disorder.
    Zellweger-like syndrome is known by only one (possibly two) described case(s), both fatal in infancy. As is evident from the name, it was similar in appearance to ZS, but was determined to be a defect of three particular enzymes and not a general loss of peroxisome function.

Peroxisomal Single-Enzyme Disorders

    These are disorders in which the peroxisome is intact and functioning, except that there is a defect in just one enzymatic process, resulting in just one primary biochemical abnormality. It doesn't necessarily follow that these diseases are any less severe than the PBDs; the loss of even a single peroxisome function is sufficient to cause disease that can closely mimic the PBDs and is every bit as severe.
    The identification of the single-enzyme disorders is ongoing. There are differences of opinion between researchers regarding the inclusion of some and/or the true nature of the defects.
    With the exception of X-ALD, all of these disorders are autosomal recessive.

X-linked adrenoleukodystrophy (X-ALD); adrenomyeloneuropathy (AMN)
[MIM No. 300100]
Peroxisomal thiolase deficiency (pseudo-Zellweger syndrome)
[MIM No. 261510]
Acyl-CoA oxidase deficiency (pseudo-NALD) [MIM No. 264470]
Bifunctional protein deficiency (sometimes this is also called
pseudo-NALD, but it is definitely distinguished from the previous)
[MIM No.261515]
DHAP-AT deficiency (pseudo-RCDP) [MIM No. 222765]
Alkyl DHAP synthase deficiency (pseudo-RCDP)
Glutaryl CoA oxidase deficiency
Mevalonate kinase deficiency
Hyperoxaluria type I (PH1) [MIM No. 259900]
Acatalasemia [MIM No. 115500]
Refsum disease (also called adult-onset or classical Refsum disease)
[MIM No.266500]

    X-ALD involves a deficiency in one of the enzymes necessary to the oxidation of the VLCFAs, which subsequently accumulate, especially in myelin and the adrenal glands. X-ALD is characterized by demyelination of the central nervous system and by disease of the adrenal glands. There are six forms (phenotypes) generally recognized, distinguished by age of onset and differences in symptoms and course: childhood cerebral, adolescent cerebral, adult cerebral, adrenomyeloneuropathy, Addison only (which affects only the adrenal glands and not the myelin, although the reason for this isn't known), and asymptomatic (or presymptomatic).
    X-ALD, by far the most common of the peroxisomal disorders, was known and studied for years before it was understood to be a peroxisomal disorder. There is extensive documentation of this disease and the various forms that it takes. It is a study in itself and there's nothing to be added here.
    Pseudo-ZS and the two forms of pseudo-NALD each involve single deficiencies of three other enzymes necessary to the oxidation of VLCFAs.  In each of them the accumulation of VLCFAs is the only (or primary) biochemical abnormality, although (as is evident from the names) they are clinically similar to the PBDs. It isn't known why this single abnormality is capable of causing such similarity. Nor is it known why X-ALD is clinically so entirely different from them, even though it also is a single-enzyme deficiency of VLCFA oxidation. It might be noted that pseudo-ZS (peroxisomal thiolase deficiency) is described from one known case.
    The two forms of pseudo-RCDP each involve single deficiencies of two enzymes necessary to the synthesis of ether-phospholipids. In each of them this impairment is the only biochemical abnormality, although clinically the diseases resemble RCDP. There is one described case each, both fatal in infancy. The DHAP-AT deficiency is also reported in cases in which there is no rhizomelia, but are otherwise indistingushable from this form of pseudo-RCDP.
    Glutaryl CoA oxidase is a peroxisome enzyme necessary to the oxidation of glutaric acid. Deficiency of the enzyme leads to accumulation of this acid, a condition known as glutaric aciduria. Type 1 and type 2 are mitochondrial disorders caused by similar deficiencies. The peroxisome enzyme deficiency represents a third type; its description is based on one known case.
    A kinase is an enzyme that converts a protein into an enzyme. Mevalonate kinase in the peroxisome is involved in one of the initial steps in the synthesis of isoprenoids (cholesterol, steroids, and related substances). Mevalonate kinase deficiency results in the impairment of this synthesis. Clinically, it has characteristics resembling other peroxisomal disorders: facial dysmorphia, enlargement of liver and spleen, cataracts, hypotonia, and profound developmental delay. It is also associated with disease of the lymph nodes, anemia, and malabsorption of fats. At its most severe it is fatal in infancy, although all patients are not affected the same by this deficiency and it does take somewhat milder forms.
    Hyperoxaluria type I (PH1) results from a deficiency in a peroxisome enzyme involved in the metabolism of glyoxylate, the end result of the dysfunction being the abnormal accumulation of calcium oxalate crystals in various organs and tissue. PH1 is associated with kidney disease, kidney and urinary tract stones, hydrocephaly, some types of eye disease, malformation of bones, and abnormal skin pigmentation. (PH2 is a similar disorder of glyoxylate metabolism, although less severe. It is not a peroxisomal disorder, being a deficiency in an enzyme normally at work in the cytosol.)
    Acatalasemia is a deficiency in the enzyme catalase, by which hydrogen peroxide (itself a product of the peroxisomal oxidation of fatty acids) is decomposed to oxygen and water. An accumulation of hydrogen peroxide would rapidly kill the cell and this decomposition is essential to its viability. The term specifically applies to the absence of the enzyme in the peroxisome, which is its proper location. The disorder itself is generally quite benign, which points to the fact that even though the enzyme is absent from the peroxisome, the process itself is taking place somewhere else in the cell. This is also the case with the PBDs.
    Refsum disease is a progressive disease of the central nervous system.  It is almost always associated with retinal or other eye disease (especially retinitis pigmentosa) and various neurologic abnormalities, and often with sensorineural hearing loss, heart arrhythmia due to the nerve dysfunction, and abnormalities of bone, cartilage, and skin. The first signs of Refsum disease, typically the progressive eye disease and ataxia (irregular and imprecise motor control), are usually not apparent until the teens or twenties. Its full progression may take another twenty or thirty years.
    Refsum disease is characterized by an impairment in the oxidation of phytanic acid and its subsequent accumulation in organs and the nervous system. The oxidation of phytanic acid is a process in which both the peroxisomes and the mitochondria take part. The classification of Refsum disease is a technical question of localizing the defective step to one or the other, and there is apparently not universal agreement that it is a peroxisomal disorder.
    As with most of the biochemical abnormalities present in the peroxisomal disorders, it is not understood precisely why the accumulation of phytanic acid leads to the pathologies of Refsum disease. In Refsum disease the limitation of phytanic acid (or its precursor, phytol) is a widely practiced dietary therapy, and pretty well documented as being effective in controlling some of the disease's progression. There is no particular evidence that such limitation has the same beneficial effect in cases of IRD or the other PBDs.

A note on the leukodystrophies -

Some peroxisomal disorders are leukodystrophies;
some leukodystrophies are peroxisomal disorders.

    The generally accepted, and more inclusive, definition of the leukodystrophies is that they are disorders in which there exists some defect in the formation or maintenance of myelin. Sometimes one encounters a narrower definition where only disorders involving active demyelination are considered leukodystrophies.

A note on deafblindness -
    The medical literature relating to the peroxisomal disorders does not use the term or concept of deafblindness to describe cases in which there are combined vision and hearing impairments. It is (understandably) not a medical concept, but without it the nature of the disability cannot be understood.

A note on form -
    The genetics and chemistry of the peroxisome is incredibly complex, and the subject obviously does not lend itself well to a "general and non-technical" discussion. This paper is intended only as an overview, and took the course of sidestepping the complexities. It needs to be emphasized that these diseases cannot be understood in a vague and oversimplified manner.
    In general, I've tried to avoid going out on any limbs, and where the information is sketchy, it is hopefully free of outright error. On this point especially, I would ask anyone reading this who finds error to not hesitate to bring it to my attention, so that appropriate correction can be made.

Acknowledgements -
    Dr Robert Steiner of Oregon Health Sciences University read the manuscript and offered his valuable opinions for change or rewording of some sections. I'm grateful to him for editing this. I'm also especially mindful to state, EXPRESSLY, that Dr Steiner bears no responsibility for any portion of this paper, or any statement made, or any errors of fact.  The content of this paper is entirely the responsibility of the author.
    My thanks to Dr Will Pitkin, a professor of English and linguistics at Utah State University (Logan), for reading and editing this manuscript. It was important to get feedback from someone who didn't already know what a peroxisome was, and  his suggestions with an aim to clarity have been very helpful. Thanks, Will.
    I'd like to thank Dr Gerald Raymond at Johns Hopkins for the time he has taken, in conversation and correspondence, to play 20 questions. I'd also like to thank Dr Richard Weleber, Casey Eye Institute OHSU, for providing me with a pre-publication draft of his own paper on the peroxisomal disorders and so much helpful explanation over the years.
    And fondest love for Mary, for the interpretation of dreams.

John Harris
jmharr@aracnet.com
26 June, 1998

revised:  08-04-98; 08-27-98; 10-13-98; 02-09-99; 09-27-99; 03-05-00
(Please note: these revision dates refer to revisons in the above text; the date of the most current addition to the following reference materials is reflected by the "Latest Update" at the end of this page.)

Sources and references -

The references and artciles listed here have been placed into broad, general categories as (hopefully) an aid to study and understanding. However, it should be borne in mind that the genetics, assembly, and structure; and the multiple metabolic functions of the peroxisome are in reality an integrated whole, and that the assignment of a reference to one category or another is sometimes entirely arbitrary.

The articles themselves are included for their apparent value as general reference or tutorial. Articles dealing, for instance, with the technical specifics of laboratory methodology, blot analysis, etc. are not typically included; it being felt that such discussions are on a level of detail not important to the general reader. For the most part, the articles were chosen as they relate to human peroxisomes and peroxisome function, as peroxisome function in other animals is not always identical to the human, and it may be potentially misleading to extrapolate from one to the other. However, in many cases animal models provide perfectly good information and such literature has by no means been disregarded. Along the same line, a great deal of understanding has been gained from the study of plant peroxisomes (and the related organelles glyoxysomes) and several articles relating to them have also been included.

By and large, the articles within each category are arranged in descending chronological order, and such arrangement should not be taken to imply the relative importance or validity of the works themselves. It may at times be true that a more recent article will represent an improved understanding on an older one; however this is not always necessarily the case, and some of the older articles on basic peroxisome function (for example, the beta-oxidation of fatty acids) are as valid today as they ever were.

X-linked ALD (including AMN) is a peroxisomal disorder of which there has been considerable study and documentation for many years. Only a very few references regarding it have been included: hopefully just enough to tie into the bigger picture.
The general texts listed at the end are included simply as being representitive. There are of course any number of  books on cell biology and biochemistry which may be usefully consulted.

INDEX

PEROXISOMAL DISORDERS
- General
- Neuropathy and Epilepsy
- Neuronal Migration Defects

PEROXISOME FUNCTION AND BIOCHEMISTRY
- General
- Ether-Phospholipid (Plasmalogen) Synthesis
- Cholesterol and Dolichol Synthesis
- Adrenal Steroid Synthesis
- Peroxisomal beta-Oxidation
- beta-Oxidation of Cholesterol (Bile Acid Synthesis)
- Phytanic Acid alpha-Oxidation
- Pipecolic Acid Oxidation (Lysine Metabolism)
- Eicosanoid (Prostanoid and Leukotriene) Oxidation
- Other Peroxisomal Oxidation Processes:
   - General
   -  Polyamines (Spermine and Spermidine)
   - D-Amino Acids
   - Purines
- Degradation of Hydrogen Peroxide and Oxygen Free Radicals
- Cell Signalling and Regulation

PEROXISOME STRUCTURE AND ASSEMBLY

GENETICS
- General
- PEX Genes and Peroxins:

PEX1       PEX7
PEX2       PEX8
PEX3       PEX9
PEX4       PEX10
PEX5       PEX11
PEX6       PEX12

PEX13      PEX20
PEX14      PEX21
PEX15      PEX22
PEX16      PEX23
PEX18
PEX19
 

PEROXISOME BIOGENESIS DISORDERS

- Zellweger syndrome (Cerebro-hepato-renal syndrome) (ZS)
- Neonatal adrenoleukodystrophy (NALD)
- Infantile Refsum disease (IRD)
- Rhizomelic chondrodysplasia punctata (RCDP type1)

- Pipecolic acidemia
- Others, not readily classified

PEROXISOME SINGLE-ENZYME DISORDERS

- Fatty acid beta-oxidation:
  - X-linked adrenoleukodystrophy (X-ALD); Adrenomyeloneuropathy (AMN)
  - Pseudo-Zellweger syndrome (thiolase deficiency)
  - Pseudo-NALD (acyl-CoA oxidase deficiency)
  - Pseudo-NALD (bifunctional enzyme deficiency)
  - Others
- Ether-phospholipid (and plasmalogen) synthesis:
  - RCDP type 2 (DHAP-AT deficiency)
  - RCDP type 3 (Alkyl-DHAP synthase deficiency)
- Other single-enzyme disorders:
  - Glutaric aciduria type 3 (Glutaryl-CoA oxidase deficiency)
  - Mevalonic aciduria (Mevalonate kinase deficiency)
  - Primary hyperoxaluria type 1 (PH1)
  - Acatalasemia
  - Refsum disease

N-3 and N-6 FATTY ACIDS
- General
- Docosahexaenoic acid (DHA)
- Arachidonic acid and the Eicosanoids
 
OTOLOGY

OPHTHALMOLOGY

DIET AND NUTRITION

MISCELLANEOUS
- Peroxisome proliferators
- Vitamin K

GENERAL TEXTS

- - -
- - -
PEROXISOMAL DISORDERS - GENERAL

The Peroxisome Biogenesis Disorders (pp. 3181-3218, in)
The Metabolic and Molecular Basis of Inherited Disease
(Scriver et al., editors), McGraw-Hill, 2001
Gould, Raymond, Valle

Advances in Human Genetics, Volume 21, Harris and Hirschorn, eds
Plenum Press, New York, 1993
Chapter 1, Peroxisomal Disorders
Hugo Moser

Genetic Diseases of the Eye, Traboulsi, editor
Oxford University Press, 1998
Chapter 33,  Peroxisomal Disorders
Richard Weleber

Peroxisomal Disorders: Genotype, Phenotype,
Major Pathological Lesions, and Pathogenesis
Powers and Moser
Brain Pathology, Vol. 8, No. 1, 101-120, January 1998

Handbook of Clinical Neurology, Volume 22 (66) :
Neurodystrophies and Neurolipidoses, Moser, editor,
Elsevier Science, 1996
Chapter 23, Generalized peroxisomal disorders and
disorders of peroxisomal fatty acid oxidation
Wanders, Heymans, Schutgens, Barth

Peroxisomal Disorders: Post- and Prenatal Diagnosis Based on a New
Classification with Flowcharts
Wanders et al.
International Pediatrics, Vol. 11, No. 4,  208-214, 1996

Peroxisomal disorders: a review
Wanders et al.
Journal of Neuropathologic Experimental Neurology
54:726-739, 1995

Disorders of Peroxisome Biogenesis
Braverman et al.
Human Molecular Genetics
Vol. 4, Review, 1791-1798, 1995

Peroxisomal disorders: a review
Fournier et al.
Journal of Inherited Metabolic Disease
17:470-486, 1994

Peroxisomal Disorders: Neurodevelopmental and Biochemical Aspects
Brown et al.
American Journal of the Diseases of Childhood, 147:617-626, 1993

Peroxisomal disorders
Moser et al.
Biochemical Cell Biology, 69:463-474, 1991

Peroxisomal disorders: A newly recognized group of genetic diseases
Schutgens et al.
European Journal of Pediatrics, 144: 430-440, 1986

Peroxisomal disorders: A newly recognized group of genetic diseases
Schutgens et al.
European Journal of Pediatrics, 144: 430-440, 1986

Peroxisomal Disorders: A Review of a Recently Recognized
Group of Clinical Entities
Talwar and Swaiman
Clinical Pediatrics
Vol. 26, No. 10, 497-504, October 1987
 
New Approaches in Peroxisomal Disorders
Moser
Dev. Neurosci. 9:1-18, 1987

Peroxisomal disorders: A newly recognized group of genetic diseases
Schutgens et al.
European Journal of Pediatrics, 144: 430-440, 1986
 
[Return to Index]

- - -
Neuropathy and Epilespy
 
Normal and Defective Neuronal Membranes:
Structure and Function; Neuronal Lesions in
Peroxisomal Disorders
James Powers
Journal of Molecular Neuroscience, 16:285-287, 2001

Epilepsy in Peroxisomal Diseases
Takahashi et al.
Epilepsia, Vol. 38, No. 2, 182-188, 1997

Globoid Cells, Glial Nodules, and Peculiar Fibrillary Changes
in the Cerebro-Hepato-Renal Syndrome of Zellweger
de Leon et al.
Annals of Neurology, Vol.2, No. 6, 473-484, December 1977

Advances in Neurology, volume 44, edited by Delgado-Escueta et al.
Basic Mechanisms of the Epilepsies: Molecular and Cellular Approaches
Delgado-Escueta et al.
Raven Press, New York, 1986

[Return to Index]

- - -
Neuronal Migration Defects

Neuronal Migration Disorder in Zellweger Mice
Is Secondary to Glutamate Receptor Dysfunction
Gressens et al.
Annals of Neurology
Vol. 48, No. 3, 336-343, September 2000

Targeted Deletion of the PEX2 Peroxisome Assembly Gene
in Mice Provides a Model for Zellweger Syndrome, a
Human Neuronal Migration Disorder
Faust and Hatten
Journal of Cell Biology
Vol. 139, No. 5, 1293-1305, December 1997

Structural and Chemical Alterations in the Cerebral
Maldevelopment of Fetal Cerbro-Hepato-Renal
(Zellweger) Syndrome
Powers et al.
Journal of Neuropatholgy and Experimental Neurology
Vol. 48, No. 3, 270-289, May 1989

Neuronal lipidosis and neuroaxonal dystrophy in
cerebro-hepato-renal (Zellweger) syndrome
Powers et al.
Acta Neuropathologica, 73:333-343, 1987

The Mechanism of Arrest of Neuronal Migration in the
Zellweger Malformation
Evrard et al.
Acta Neuropathologica, 41:109-117, 1978

[Return to Index]
- - -
PEROXISOME FUNCTION AND BIOCHEMISTRY

General

Biochemistry of peroxisomes in health and disease
Singh
Molecular and Cellular Biochemistry, 167:1-29, 1997

The Cytochrome P450 4 (CYP4) Family
Simpson
General Pharmacology, Vol 28, No. 3, 1997

Peroxisomal Lipid Metabolism
Reddy and Mannaerts
Annual Review of Nutrition, 14:343-370, 1994

Metabolic pathways in mammalian peroxisomes.
Mannaerts and van Veldhoven
Biochimie, Vol 73, Nos. 3-4, 147-158, 1993
 
Biochemistry of peroxisomes
van den Bosch et al.
Annual Review of Biochemistry
61:157-197, 1992

The peroxisome: functional properties
in health and disease
Mannaerts and van Veldhoven
Biochemical Society (Great Britain) Transcripts
Vol. 18, No. 1, 87-89, February 1990
 
The role of peroxisomes in mammalian cellular metabolism
Lazarow
Journal of Inherited Metabolic Disorders
Vol. 10, Supplement 1, 11-22, 1987

[Return to Index]

- - -
Ether-Phospholipid (Plasmalogen) Synthesis

Glycerolipid Biosynthesis in
Peroxisomes (Microbodies)
Amiya K. Hajra
Prog. Lipid Res., Vol 34, No. 4, 343-364, 1995

Lipid Biosynthesis in Peroxisomes
Hajra and Das
Annals of the New York Academy of Science, 1993

Ether lipid synthesis and its deficiency
in peroxisomal disorders
van den Bosch et al.
Biochimie, 75: 1830189, 1993

Essential fatty acids and serine as plasmalogen precursors
in relation to competing metabolic pathways
Cook, Thomas, and Xu
Biochemical Cell Biology 69:475-484, 1991

Glyceryl ethers in peroxisomal disease
Poulos et al.
Clinical Genetics 39:13-25, 1991

Topography of ether phospholipid biosynthesis
Hardeman and van den Bosch
Biochimica et Biophysicia Acta, 1006:1-8

Aberration in De Novo Ether Lipid Biosynthesis
in Peroxisomal Disorders
van den Bosch et al.
Biological Membranes: Aberrations in Membrane
Structure and Function, pgs 139-150, 1988
(Alan R. Liss, Inc.)

Glycerolipid biosynthesis in peroxisomes via the
acyl-dehydroxyacetone phosphate pathway
Hajra and Bishop
Annals of the New York Academy of Sciences
386:170-182, 1982

[Return to Index]

- - -
Cholesterol and Dolichol Synthesis

Analysis of isoprenoid biosynthesis in
peroxisomal-deficient Pex2 CHO cell lines
Aboushadi and Krisans
Journal of Lipid Research, 39:1781-1791, 1998

Differential Deficiency of Mevalonate Kinase and
Phosphomevalonate Kinase in Patients with Distinct
Defects in Peroxisome Biogenesis
Wanders and Romeijn
Biochemical and Biophysical Research Communications
Vol 247, No. 3, 663-667, 1998

Mevalonate Kinase is Predominately Localized in Peroxisomes
and Is Defective in Patients with Peroxisome Deficiency Disorders
Biardi et al.
Journal of Biological Chemistry, Vol. 269, No. 2, 1197-1205
January 1994

Peroxisomal cholesterol synthesis in vivo
Hashimoto and Hayashi
Biochimica et Biophysica Acta, 1214:11-19, 1994

Biosynthesis of Dolichol and Cholesterol
in Rat Liver Peroxisomes
Ericsson et al.
Biochimie, 75:167-173, 1993

Presence of Individual Enzymes of Cholesterol
Biosynthesis in Rat Liver Peroxisomes
Appelkvist et al.
Archives of Biochemistry and Biophysics
Vol. 282, No. 2, 318-325, December 1991

Normal Cholesterol Synthesis in Human Cells
Requires Functional Peroxisomes
Hodge et al.
Biochemical and Biophysical Research Communications
Vol. 181, No. 2, 537-541, Dec 16, 1991

Lipoprotein[a] is not present in the plasma of
patients with some peroxisomal disorders
van der Hoek et al.
Journal of Lipid Research, 38:1612-1619, 1997

Plasma Lipoproteins and Monocyte Macrophages in a
Peroxisome-Deficient System: Study of a Patient with
Infantile Refsum Disease
Mandel et al.
Journal of Inherited Metabolic Disease
15:774-784, 1992

[Return to Index]

- - -
Adrenal Steroid Synthesis

Peroxisomes in Adrenal Steroidogenesis
Magalhaes and Magalhaes
Microscopy Research and Technique 36: 493-502 (1997)

Sterol Carrier Protein 2:
A Role in Steroid Hormone Synthesis?
Pfiefer et al.
Journal of Steroid Biochemistry and Molecular Biology
Vol. 47, No. 1-6, 167-172 (1993)
- - -

Peroxisomal beta-Oxidation

Peroxisomal fatty acid alpha- and beta-oxidation in humans:
peroxisomal metabolite transporters and peroxisomal diseases
Wanders et al.
Biochemical Society Transactions
Vol. 29, Part 2, 250-267, 2001

Peroxisomal beta-Oxidation Enzymes
Takashi Hashimoto
Neurochemical Research
Vol. 24, No. 4, 551-563, 1999

Metabolic aspects of peroxisomal beta-oxidation
Osmundsen et al.
Biochimica et Biophysica Acta, 1085:141-158, 1991

Pathophysiology of peroxisomal beta-oxidation
Vamecq and Draye
Essays in Biochemistry, 24:115-225, 1989

Peroxisomal Fatty Acid beta-Oxidation
in Relation to Adrenoleukodystrophy
Wanders and Tager
Dev Neurosci 13:262-266, 1991

Role of Peroxisomal Fatty Acyl-CoA beta-Oxidation
in Phospholipid Biosynthesis
Hayashi and Takahata
Archives of Biochemistry and Biophysics
Vol. 284, No. 2, 326-331, 1996

Phospholipid transfer proteins revisited
Karel Wirtz
Biochemical Journal, 324:353-360, 1997

Peroxisomal beta-oxidation of polyunsaturated
fatty acids
Hiltunen et al.
Biochimie 75, 175-182, 1993

Properties of Peroxisomal 3-Ketoacyl-CoA Thiolase
from Rat Liver
Miyazawa et al.
Journal of Biochemistry, Vol. 90, No. 2, 511-519, 1981

[Return to Index]

- - -
beta-Oxidation of Cholesterol (Bile Acid Synthesis)

Inborn Errors of Metabolism with Consequences
for Bile Acid Synthesis
Bjorkhem
Scandanavian Journal of Gastroenterology
29 Suppl 204:68-72, 1994

Peroxisomal oxidation of the steroid side chain
in bile acid formation
Pedersen
Biochimie, 75:159-165, 1993

Inborn Errors of Bile Acid Metabolism
Clayton
Journal of Inherited Metabolic Disease
14:478-496, 1991

Role of liver peroxisomes in bile acid formation:
Inborn error of C27-steroid side chain cleavage
in peroxisome deficiency (Zellweger syndrome)
Kase
Scandanavian Journal of Clinical Laboratory Investigation
49:1-10, 1989

Defective Peroxisomal Cleavage of the C27-Steroid Side Chain
in the Cerebro-Hepato-Renal Syndrome of Zellweger
Kase et al.
Journal of Clinical Investigation
Vol. 75, 427-435, February 1985

[Return to Index]

- - -
Phytanic Acid alpha-Oxidation

Phytanic acid oxidation: normal activation and transport yet
defective alpha-hydroxylation of phytanic acid in peroxisomes
from Refsum disease and rhizomelic chondrodysplasia punctata
Pahan et al.
Journal of Lipid Research, 37:1137-1143, 1996

Phytanic acid oxidation: topographical localization of
phytanoyl-CoA ligase and transport of phytanic acid into
human peroxisomes
Pahan and Singh
Journal of Lipid Research, 36:986-997, 1995

2-Hydroxyphytanic acid oxidase activity in rat and human liver
peroxisomes and its deficiency in the Zellweger syndrome
Biochimica et Biophysica Acta, 1227:177-182, 1994

Pristianic acid and phytanic acid in plasma
from patients with peroxisomal disorders
Ten Brink et al.
Journal of Lipid Research, 33:41-47, 1992

[Return to Index]

- - -
Pipecolic Acid Oxidation (Lysine Metabolism)

L-Pipecolic acid oxidase, a human enzyme essential
for the degradation of L-pipecolic acid, etc.
Dodt et al.
Biochemical Journal, 345:487-494, 2000

Molecular Cloning and Expression of
Human L-Pipcolate Oxidase
IJlst et al.
Biochemical and Biophysical Research Communications
270:1101-1105, 2000

Pipecolic Acid is Oxidized by Renal and Hepatic Peroxisomes:
Implications for Zellweger's Cerebro-hepatic-renal Syndrome (CHRS)
Zaar et al.
Experimental Cell Research
164:267-271, 1986

L-Pipecolaturia in Zellweger syndrome
Lam et al.
Biochimica et Biophysica Acta
882:254-257, 1986

[Return to Index]

- - -
Eicosanoid (Prostanoid and Leukotriene) Oxidation

Impaired degradation of prostaglandins and
thromboxane in Zellweger syndrome
Fauler et al.
Pediatric Research
Vol. 36, No. 4, 449-455, October 1994

Impaired degradation of leukotrienes in patients
with peroxisome deficiency disorders
Mayatepek et al.
Journal of Clinical Investigation, 91:881-888, 1993

Role of peroxisomes in the degradation of prostaglandins
Diczfalusy and Alexson
Progress in Clinical Biology Research, 375:253-261, 1992

Metabolism of prostaglandin F2 alpha in Zellweger syndrome.
Peroxisomal beta-oxidation is a major importance for in vivo
degradation of prostaglandins in humans
Diczfalusy et al.
Journal of Clinical Investigation
Vol 88, No. 3, 978-984, September 1991

Peroxisomal degradation of leukotrienes by
beta-oxidation from the omega-end.
Jedlitschky et al.
Journal of Biological Chemistry, 266:24763-24772, 1991

[Return to Index]

- - -
Other Peroxisomal Oxidation Processes:

- General

In situ heterogeneity of peroxisomal oxidase activities:
an update.
Van den Munckhof
Histochemical Journal
Vol. 28, No. 6, 401-429, June 1996

Peroxisome oxidases: cytochemical localization and
biological relevance
Angermuller
Progress of Histochemistry and Cytochemistry
Vol. 20, No. 1, 1-65, 1989

[Return to Index]

- - -
- Polyamines (Spermine and Spermidine)

Primary structure and expression of peroxisomal
acetylspermidine oxidase in the methylotrophic yeast
Candida boidinii.
Nishikawa et al.
Federation of European Biochemical Societies Letters
Vol. 476, No. 3, 150-154, July 2000

In situ substrate specificity and ultrastructural localization
of polyamine oxidase activity in unfixed rat tissues.
Van den Munckhof et al.
Journal of Histochemistry and Cytochemistry
Vol. 43, No. 11, 1155-1162, November 1995

Urinary polyamine and metabolite excretion
by children with Zellweger's syndrome.
Govaerts et al.
Chimie Clinique Acta
Vol. 192, No. 1, 67-67, November 1990

[Return to Index]

- - -
- D-Amino Acids
d-amino acid oxidase [McKusick No. 124050]
 
Molecular cloning and sequence analysis of cDNA
encoding human kidney D-amino acid oxidase
Momoi et al.
Federation of European Biochemical Societies Letters
Vol. 238, No. 1, 180-184, September 1988

Ultrastructural Localization of D-Amino Acid Oxidase in
Microperoxisomes of the Rat Nervous System
Arnold, Liscum, Holtzman
Journal of Histochemistry and Cytochemistry
Vol. 27, No. 3, 735-745, 1979
 
WIS GeneCard:
(d-amino acid oxidase)  DAO
http://bioinfo.weizmann.ac.il/cards-bin/carddisp?DAO

[Return to Index]

- - -
- Purines

Peroxisomal purine metabolism
Yeldandi et al
Annals of the New York Academy of Sciences
804:165-175, December 1996

[Return to Index]

- - -
Degradation of Hydrogen Peroxide
and Oxygen Free Radicals

Mammalian peroxisomes: metabolism of oxygen and
reactive oxygen species
Singh
Annals of the New York Academy of Sciences
804:612-627, December 1996

Abnormality of Translational Regulation of Catalase
Expression in Disorders of Peroxisome Biogenesis
Singh et al.
Journal of Neurochemistry, 67:2373-2378, 1996

Human disease, free radicals, and the
oxidant/antioxidant balance
McCord
Clinical Biochemistry, 26:351-357, 1993

Peroxisomal participation in the cellular response
to oxidative stress of endotoxin
Dhaunsi et al.
Molecular and Cellular Biochemistry, 126:25-35, 1993

Isolation and characterization of the human
catalase gene
Quan et al.
Nucleic Acids Research, 14:5321, 1986

On the relative rates of synthesis and degradation
of catalase in vertebrate tissues
Crane et al.
International Journal of Biochemistry, 9:589-596, 1978

[Return to Index]

- - -
Cell Signalling and Regulation

Cellular Signalling: the Role of the Peroxisome
Masters
Cellular Signalling, Vol 8. No.3, 197-208, 1997

On the role of the peroxisome in cell differentiation
and carcinogenesis
Masters and Crane
Molecular and Cellular Biochemistry
187:85-97, 1998

Neuroactive steroids: mechanisms of action and
neuropharmacological perspectives
Rupprecht and Holsboer
Trends in Neuroscience, Vol.22, No. 9, 410-416, 1999

Fatty Acids and Brain Peptides
Yehuda et al.
Peptides, Vol 19, No. 2, 407-419, 1998

[Return to Index]

- - -
PEROXISOME STRUCTURE AND ASSEMBLY
 
Peroxisomal Protein Import: The Paradigm Shifts
Smith and Schnell
Cell, 105:293-296, 04 May 2001

Components Involved in Peroxisome Import, Biogenesis,
Proliferation, Turnover, and Movement
Subramani
Physiological Reviews, Vol. 78, No. 1, 171-188, 1998
 
The surprising complexity of peroxisome biogenesis
Laura Olsen
Plant Molecular Biology 38:1630189, 1998

Peroxisome Biogenesis
Waterham and Cregg
BioEssays (ISCU Press)
Vol. 19, No. 1, 57-66, 1997

Proteins involved in peroxisome biogenesis and functioning
Elgersma and Tabak
Biochimica et Biophysica Acta, 1286: 269-273, 1996
 
The cytosolic and membrane components required
for peroxisome protein import
Terlecky et al.
Experientia 52:1050-1054, 1996

The targeting and assembly of peroxisomal proteins
McNew and Goodman
Trends in Biochemical Science
21:54-58, February 1996
 
Identification of three distinct peroxisomal protein import defects
in patients with peroxisome biogenesis disorders
Slawecki et al.
Journal of Cell Science, 108: 1817-1829, 1995
 
How proteins penetrate peroxisomes
Rachubinski and Subramani
Cell, 83:525-528, 1995

Identification of Peroxisomal Membrane Ghosts with an
Epitope-Tagged Integral Membrane Protein in Yeast Mutants
Lacking Peroxisomes
Purdue and Lazarow
Yeast 11:1045-1060, 1995

Peroxisome Structure, Function and Biogeneis -
Human Patients and Yeast Mutants Show Strikingly
Similar Defects in Peroxisome Biogensis
Paul Lazarow
Journal of Neurolpathology and Experimental Neurology
Vol. 54, No. 5, 720-725, September 1995

Characterization of Human Peroxisomal Membrane Proteins
Santos et al.
Journal of Biological Chemistry
Vol. 269, No. 40, October 1994

Differential Protein Import Deficiencies in
Human Peroxisome Assembly Disorders
Motley et al.
Journal of Cell Biology, Vol. 125, No. 4, May 1994
 
Protein Import into Peroxisomes and
Biogenesis of the Organelle
Subramani
Annual Review of Cell Biology, No. 9, 445-478, 1993
 
Proteins and enzymes of the peroxisomal membrane in mammals
Causeret et al.
Biol Cell 77: 89-104, 1993
 
Identification of Peroxisomal Targeting Signals Located
at the Carboxy Terminus of Four Peroxisomal Proteins
Gould, Keller, and Subramani
Journal of Cell Biology 107:897-905, 1988

Peroxisomal Membrane Ghosts in Zellweger Syndrome -
Aberrant Organelle Assembly
Santos et al.
Science, 239:1536-1538, March 1988

Polypeptide and Phospholipid Composition
of the Membrane of Rat Liver Peroxisomes
Fujiki et al.
Journal of Cell Biology, Vol. 93, April 1982
 
[Return to Index]

- - -
GENETICS
 
Peroxisomal Disorders
Gerald Raymond
Current Opinion in Neurology
14:783-787, 2001

Peroxisomal Disorders: Genotype, Phenotype,
Major Pathololgical Lesions, and Pathogenesis
Powers and Moser
Brain Pathology, 8:101-120, 1998

A Unified Nomenclature for Peroxisome
Biogenesis Factors
Distel et al.
The Journal of Cell Biology
Vol. 135, No. 1, 1-3, October 1996

Phenotype of patients with peroxisomal disorders
subdivided into sixteen complementation groups
Moser et al.
The Journal of Pediatrics, 127:13-22, 1995

Standardization of Complementation Grouping
of Peroxisome-deficient Disorders, &c.
Shimozawa et al.
American Journal of Human Genetics, 52:843-844, 1993

[Return to Index]

- - -
PEX Genes and Peroxins:

PEX1
[McKusick No. 602136]

Disorders of Peroxisome Biogenesis Due to Mutations in PEX1:
Phenotypes and PEX1 Protein Levels
Walter et al.
American Journal of Human Genetics, 69:35-48, 2001

The Peroxisome Biogenesis Factors Pex4p, Pex22p, Pex1p, and Pex6p
Act in the Terminal Steps of Peroxisomal Matrix Protein Import
Collins et al.
Molecular and Cellular Biology
Vol. 20, No. 20, 7816-7826, October 2000

A common PEX1 frameshift mutation in patients with disorders of
peroxisome biogenesis correlates with the severe Zellweger syndrome phenotype
Maxwell et al.
Human Genetics, 105:38-44, 1999

Identification of a Common PEX1 Mutation in Zellweger Syndrome
Collins and Gould
Human Mutation, 14:45-53, 1999

Mutations in PEX1 in peroxisome biogenesis disorders:
G843D and a mild clinical phenotype
Gartner et al.
Journal of Inherited Metabolic Disease, 22:311-313, 1999

Disorders of peroxisome biogenesis: Complementation analysis shows genetic
heterogeneity with strong overrepresentation of one group (PEX1 deficiency)
Wanders et al.
Journal of Inherited Metabolic Disease, 22:314-318, 1999

Disruption of a PEX1-PEX6 interaction is the most common cause of the
neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy,
and infantile Refsum disease
Geisbrecht et al.
Proceedings of the National Academy of Sciences (USA)
Vol. 95, 8630-8636, 1998

Mutations in PEX1 are the most common cause
of peroxisome biogenesis disorders
Reuber et al.
Nature Genetics, Vol. 17, 445-448, December 1997

Human PEX1 is mutated in complementation group 1
of the peroxisome biogensesis disorders
Portsteffen et al.
Nature Genetics, Vol 17, 449-452, December 1997

WIS GeneCard:
PEX 1   http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PEX1

Peroxisome Website, Johns Hopkins: PEX1
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/pex1text.html
 
[Return to Index]

- - -
PEX2
[McKusick No. 170993]

Genomic Organization and Characterization of Human
PEX2 Encoding a 35-kDa Peroxisomal Membrane Protein
Biermanns and Gartner
Biochemical and Biophysical Research Communications
Vol. 273, No. 3, 985-990, 2000

A Missense Mutation in the RING Finger Motif of PEX2
Protein Disturbs the Import of Peroxisomal Targeting Signal 1
(PTS1)-Containing Protein but Not the PTS2-Containing Protein
Huang et al.
Biochemical and Biophysical Research Communications
Vol. 270, No. 3, 717-721, 2000

Molecular Mechanism of Detectable Catalase-Containing Particles,
Peroxisomes, in Fibroblasts from a Pex2-Defective Patient
Shimozawa et al.
Biochemical and Biophysical Research Communications
Vol. 268, No. 1, 31-35, 2000

Functional Identification of a Leishmania Gene Related to the
Peroxin 2 Gene Reveals a Common Ancestry of Glycosomes
and Peroxisomes
Flahspohler et al.
Molecular and Cellular Biology
Vol. 17, No. 3, 1093-1101, March 1997

WIS GeneCard:
PEX2  (peroxisomal membrane protein 3; PXMP3)
http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PXMP3

Peroxisome Website, Johns Hopkins: PEX2
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/PEX2text.html

[Return to Index]

- - -
PEX3
[McKusick No. 603164]

Identification of PEX3 as the gene mutated in a Zellweger syndrome
patient lacking peroxisomal remnant structures
Shimozawa et al.
Human Molecular Genetics
Vol. 9, No. 13, 1995-1999, 2000

The Human PEX3 Gene Encoding a Peroxisomal Assembly Protein:
Genomic Organization, Positional Mapping, and Mutation Analysis
in Candidate Phenotypes
Muntau et al.
Biochemical and Biophysical Research Communications
Vol. 268, No. 3, 704-710, 2000

Defective Peroxisome Membrane Synthesis Due to Mutations in
Human PEX3 Causes Zellweger Syndrome,
Complementation Group G
Muntau et al.
American Journal of Human Genetics, 67:967-975, 2000

PEX3 is the Causal Gene Responsible for Peroxisome Membrane
Assembly-Defective Zellweger Syndrome of
Complementation Group G
Ghaedi et al.
American Journal of Human Genetics, 67:976-981, 2000

Indentification and characterization of
the human peroxin PEX3
Soukupova et al.
European Journal of Cell Biology
78:357-374, June 1999

Cloning and characterization of the gene encoding the
human peroxisomal assembly protein Pex3p
Kammerer et al.
Federation of European Biochemical Societies Letters
429:53-60, 1998

WIS GeneCard:
PEX3      http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PEX3

Peroxisome Website, Johns Hopkins: PEX3
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/PEX3text.html
 
[Return to Index]

- - -
PEX 4

Pex22p of Pichia pastoris, Essential for Peroxisomal Matrix Import,
Anchors the Ubiquitin-conjugating Enzyme, Pex4p, on the
Peroxisomal Membrane
Koller et al.
Journal of Cell Biology
Vol. 146, No. 1, 99-112, 12 July 1999

The Ubiquitin-conjugating enzyme Pex4p of Hansenula polymorpha
is required for efficient functioning of the PTS1 import machinery
van der Klei et al.
European Molecular Biology Organization Journal
Vol. 17, No. 13, 3608-3618, 1998

The Pichia pastoris PAS4 Gene Encodes a Ubiquitin-conjugating
Enzyme Required for Peroxisome Assembly
Crane et al.
Journal of Biological Chemistry
Vol. 269, No. 34, 21835-21844, 26 August 1994

Peroxisome Website, Johns Hopkins: PEX4
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/PEX4text.html

[Return to Index]

- - -
PEX 5
[McKusick No. 600414]

A Proposed Model for the PEX5-Peroxisomal Targeting
Signal-1 Recognition Complex
Gatto et al.
Proteins; Structure, Function, and Genetics
38:241-246, 2000

Interaction of Pex5p, the Type 1 Peroxisomal Targeting
Signal Receptor, with the Peroxisomal Membrane Proteins
Pex14p and Pex13p
Urquhart et al.
Journal of Biological Chemistry
Vol. 275, No. 6, 4127-4136, 11 February 2000

Recombinant Human Peroxisomal Targeting Signal
Receptor PEX5
Schliebs et al.
Journal of Biological Chemistry
Vol 274, No. 9, 5666-5673, 26 February 1999

Identification of a human PTS1 receptor docking protein
directly required for peroxisomal protein import
Fransen et al.
Proceeds of the National Academy of Sciences (USA)
95:8087-8092, July 1998

Human Peroxisomal Targeting Signal-1 Receptor Restores
Peroxisomal Protein Import in Cells from Patients with
Fatal Peroxisomal Disorders
Wiemer et al.
Journal of Cell Biology
Vol. 130, No. 1, Pg. 51-65, July 1995

Mutations in the PTS1 receptor gene, PXR1,
define complementation group 2 of the peroxisome
biogenesis disorders
Dodt et al.
Nature Genetics, 9:115-125, February 1995

WIS GeneCard:
PEX 5 (peroxisome receptor 1; PXR1)
http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PXR1

Peroxisome Website, Johns Hopkins: PEX5
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/PEX5text.html

[Return to Index]

- - -
PEX 6
[McKusick No. 601498]

Temperature-Sensitive Mutation of PEX6 in Peroxisome
Biogenesis Disorders in Complementation Group C (CG-C):
Comparative Study of PEX6 and PEX 1
Imamura et al.
Pediatric Research, 48:541-545, 2000

Genomic Structure and Indentification of 11 Novel Mutations
of the PEX6 (Peroxisome Assembly Factor-2) Gene in
Patients with Peroxisome Biogenesis Disorders
Zhang et al.
Human Mutation, 13:487-496, 1999

Hansenula polymorpha Pex1p and Pex6p are
Peroxisome-associated AAA Proteins that
Functionally and Physically Interact
Kiel et al.
Yeast, 15:1059-1078, 1999

A Cytoplasmic AAA Family Peroxin, Pex1p,
Interacts with Pex6p
Tamura et al.
Biochemical and Biophysical Research Communications
Vol. 245, No. 3, 883-886, 1998

The peroxisome biogenesis disorder group 4 gene,
PXAAA1, encodes a cytoplasmic ATPase required
for stability of the PTS1 receptor
Yahraus et al.
European Molecular Biology Organization Journal
Vol. 15, No. 12, 2914-2923, 1996

WIS GeneCard:
PEX6      http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PEX6

Peroxisome Website, Johns Hopkins: PEX6
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/PEX6text.html

[Return to Index]

- - -
PEX 7
[McKusick No. 601757]

PEX7 Gene Structure, Altnernative Transcripts, and
Evidence for a Founder Haplotype for the Frequent
RCDP Allele, L292ter
Braverman et al.
Genomics 63:181-192, 2000

Rhizomelic Chondrodysplasia Punctata, A Peroxisomal
Biogenesis Disorder Caused by Defects in Pex7p, a
Peroxisomal Protein Import Receptor: A Minireview
Purdue et al.
Neurochemical Research
Vol. 24, No. 4, 581-586, 1999

A novel nonsense mutation of the PEX7 gene in a patient
with rhizomelic chondrodysplasia punctata
Shimozawa et al.
Journal of Human Genetics, 44:123-125, 1999

A Mobile PTS2 Receptor for Peroxisomal Protein
Import in Pichia pastoris
Elgersma et al.
Journal of Cell Biology
Vol. 140, No. 4, 807-820, 23 February 1998

Human PEX7 encodes the peroxisomal PTS2
receptor and is responsible for rhizomelic
chondrodysplasia punctata
Braverman et al.
Nature Genetics, 15:369-376, April 1997

Rhizomelic chondrodysplasia punctata is a peroxisomal
protein targeting disease caused by a non-functional
PTS2 receptor
Motley et al.
Nature Genetics, 15:377-380, April 1997

Rhizomelic chondrodysplasia punctata is caused by
deficiency of human PEX7, a homologue of the yeast
PTS2 receptor
Purdue et al.
Nature Genetics, 15:381-384, April 1997

PEB1 (PAS7) in Saccharomyces cerevisiae Encodes a
Hydrophilic, Intra-peroxisomal Protein that is a Member
of the WD Repeat Family and is Essential for the Import
of Thiolase into Peroxisomes
Zhang and Lazarow
The Journal of Cell Biology
Vol. 129, No. 1, 65-80, April 1995

WIS GeneCard
PEX7      http://bioinformatics.weizmann.ac.il/cards-bin/carddisp?PEX7

Peroxisome Website, Johns Hopkins: PEX7
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/PEX7text.html

RCDP type 1:   McKusick No. 215100

[Return to Index]

- - -
PEX8

A Role for the Peroxin Pex8p in Pex20p-dependent Thiolase Import
into Peroxisomes of the Yeast Yarrowia lipolytica
Smith and Rachubinski
Journal of Biological Chemistry
Vol. 276, No. 2, 1618-1625, 12 January 2001

Pex8p, an Intraperoxisomal Peroxin of Saccharomyces cerevisiae
Required for Protein Transport into Peroxisomes Binds the
PTS1 Receptor Pex5p
Rehling et al.
Journal of Biological Chemistry
Vol 275, No. 5, 3593-3602, 04 February 2000

Peroxisome Website, Johns Hopkins: PEX8
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/PEX8text.html

[Return to Index]

- - -
PEX 9

The Yarrowia liplytica Gene PAY2 Encodes a 42-kDa Peroxisomal
Integral Membrane Protein Essential for Matrix Protein Import, etc.
Eitzen et al.
Journal of Biological Chemistry
Vol. 270, No. 3, 1429-1436, 20 January 1995

Peroxisome Website, Johns Hopkins: PEX9
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/PEX9text.html

[Return to Index]

- - -
PEX10
[McKusick No. 602859]

Phenotype-Genotype Relationships in PEX10-Deficient
Peroxisome Biogenesis Disorder Patients
Warren et al.
Human Mutation 15:509-521, 2000

Identification of PEX10, the Gene Defective in
Complementation Group 7 of the Peroxisome-Biogenesis Disorders
Warren et al.
American Journal of Human Genetics
63:347-359, 1998

Mutations in PEX10 are the cause of Zellweger
peroxisome deficiency syndrome of complementation group B
Okumoto et al.
Human Molecular Genetics
Vol. 7, No. 9, 1399-1405, 1998

WIS GeneCard:
PEX10     http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PEX10

Peroxisome Website, Johns Hopkins: PEX10
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/pex10text.html

[Return to Index]

PEX11

[McKusick No. 603866] PEX11-alpha
[McKusick No. 603877] PEX11-beta

Pex11p Plays a Primary Role in Medium-Chain Fatty Acid
Oxidation, a Process that Affects Peroxisome Number and Size
in Saccharomyces cervisiae
van Roermund et al.
Journal of Cell Biology
Vol. 150, No. 3, 489-497, 07 August 2000

Expression of PEX11beta Mediates Peroxisome Proliferation
in the Absence of Extracellular Stimuli
Schrader et al.
Journal of Biological Chemistry
Vol. 273, No. 45, 29607-29614, 06 November 1998

Peroxisome Biogenesis: Involvement of ARF and Coatomer
Passreiter et al.
Journal of Cell Biology
Vol. 141, No. 2, 373-383, 20 April 1998

Redox-sensitive Homodimerization of Pex11p:
A Proposed Mechanism to Regulate Peroxisomal Division
Marshall et al.
Journal of Cell Biology
Vol. 135, No. 1, 123-137, October 1996

WIS GeneCard:
PEX11    http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PEX11

Peroxisome Webpage, Johns Hopkins: PEX11
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/pex11text.html

[Return to Index]

- - -
PEX12
[McKusick No. 601758]
 
PEX12 Interacts with PEX5 and PEX10 and Acts
Downstream of Receptor Docking in Peroxisomal
Matrix Protein Import
Chang et al.
Journal of Cell Biology
Vol. 147, No. 4, 761-773, 15 November 1999

PEX12, the Pathogenic Gene of Group III Zellweger Syndrome:
cDNA Cloning by Functional Complementation on a CHO Cell
Mutant, Patient Analysis, And Characterization of PEX12p
Okumoto et al.
Molecular and Cellular Biology
Vol. 18, No. 7, 4324-4336, July 1998

PEX12 encodes an integral membrane protein
of peroxisomes
Okumoto and Fujiki
Nature Genetics, 17:265-266, November 1997

Isolation of the human PEX12 gene, mutated in
group 3 of the peroxisome biogenesis disorders
Chang et al.
Nature Genetics, 15:285-288, April 1997

Multiple PEX Genes are Required for Proper Subcellular Distribution
and Stability of Pex5p, the PTS1 Receptor: Evidence that PTS1
Protein Import is Mediated by a Cycling Receptor
Dodt and Gould
Journal of Cell Biology
Vol 135, No. 6, Part 2, 1763-1774, December 1996

WIS GeneCard:
PEX12    http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PEX12

Peroxisome Website, Johns Hopkins: PEX12
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/PEX12text.html

[Return to Index]

- - -
PEX13
[McKusick No. 601789]

Pex13 is Mutated in Complementation Group 13 of the
Peroxisome-Biogenesis Disorders
Liu et al.
American Journal of Human Genetics
65:621-634, 1999

Nonsense and temperature-sensitive mutations in PEX13
are the cause of  complementation group H  of
peroxisome biogenesis disorders
Shimozawa et al.
Human Molecular Genetics, Vol. 8, No. 6, 1077-1083, 1999

Involvement of Pex13p in Pex14p Localization and
Peroxisomal Targeting Signal 2-dependent
Protein Import into Peroxisomes
Girzalsky et al.
Journal of Cell Biology
Vol. 144, No. 6, 1151-1162, March 1999

Genomic Structure of PEX13, a Candidate Peroxisome
Buigenesis Disorder Gene
Bjorkman et al.
Genomics 54, 521-528, 1998

Pex13p is an SH3 Protein of the Peroxisome Membrane
and is a Docking Factor for the Predominantly
Cytoplasmic PTS1 Receptor
Gould et al.
Journal of Cell Biology
Vol. 135, No. 1, 85-95, October 1996

The SH3 Domain of Saccharomyces cerevisiae Peroxisomal
Membrane Protein Pex13p Functions as a Docking Site for Pex5p,
a Mobile Receptor for the Import of PTS1-containing Proteins
Elgersma et al.
Journal of Cell Biology
Vol 135, No. 1, 97-109, October 1996

WIS GeneCard:
PEX13  http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PEX13

Peroxisome Website, Johns Hopkins: PEX13
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/pex13text.html

[Return to Index]

- - -
PEX14
[McKusick No. 601791]

Pex14p, a Peroxisomal Membrane Protein Binding Both
Receptors of the Two PTS-Dependent Import Pathways
Albertini et al.
Cell, Vol. 89, 83-92, April 1997

WIS GeneCard:
PEX14  http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PEX14

Peroxisome Website, Johns Hopkins: PEX14
http://www.peroxisome.org/Scientist/Biogenesis/peroxins/pex14text.html

- - -
PEX16
[McKusick No. 603360]

[Return to Index]

- - -
PEX19
[McKusick No. 600279]

PEX19 Binds Multiple Peroxisomal Membrane Proteins, is
Predominantly Cytoplasmic, and is Required for Peroxisome
Membrane Synthesis
Sacksteder et al.
Journal of Cell Biology
Vol 148, No. 5, 931-944, 06 March 2000

[Return to Index]

- - -
PEROXISOME BIOGENESIS DISORDERS [McKusick No. 601539]

Cerebro-Hepato-Renal Syndrome (CHRS)
Zellweger Syndrome (ZS)
ZWS1  [McKusick No. 214100]

ZWS2
WIS GeneCard:
ATP-binding cassette, sub-family D, member 3  ABCD3
http://bioinfo.weizmann.ac.il/cards-bin/carddisp?ABCD3
{= 70kDa peroxisomal membrane protein PMP70; aka  peroxisomal membrane protein 1 PXMP1)
[McKusick No. 170995]

ZWS3  [McKusick No. 170993]
 
Zellweger syndrome: Diagnostic assays, syndrome
delineation, and potential therapy
Wilson et al.
American Journal of Medical Genetics
24:69-82, 1986

Fatal Cerebrohepatorenal (Zellweger) Syndrome:
Dysmorphic, Radiologic, Biochemical, and Pathologic
Findings in Four Affected Fetuses
Powers et al.
Human Pathology, Vol. 16, No. 6, 610-620, June 1985
 
The cerebrohepatorenal (Zellweger) syndrome: increased levels and
impaired degradation of very-long-chain fatty acids and their use
in prenatal diagnosis
Moser et al.
New England Journal of Medicine, 310:1141-1146, 1984

The cerebrohepatorenal syndrome of Zellweger:
Morphologic and metabolic aspects
Kelley
American Journal of Medical Genetics
16:503-517, 1983

A familial syndrome of multiple congenital defects
Bowen, Lee, Zellweger
Bulletin of Johns Hopkins Hospital, 114:402-414, 1964

[Return to Index]

- - -
Neonatal Adrenoleukodystrophy [McKusick No. 202370]

Neonatal adrenoleukodystrophy: impaired plasmalogen biosynthesis
and peroxisomal beta-oxidation due to a deficiency of
catalase-containing particles (peroxisomes) in cultured
skin fibroblasts
Wanders et al.
Journal of Neurological Science, 77:331-340, 1987

Neonatal adreno-leukodystrophy: New cases, biochemical studies,
and differentiation from Zellweger and related peroxisomal
polydystrophy syndromes
Kelly et al.
American Journal of Medical Genetics, 23:869, 1986

[Return to Index]

- - -
Infantile Refsum Disease [McKusick No. 266510]

Clinical Neurology, Volume 4, Joynt (editor)
J.B. Lippincott Comapny, Philadelphia, 1992
Chapter 56 - Inborn Errors Affecting the Nervous System
Infantile Refsum Disease, pg 45

Magnetic Resonance Findings in Infantile Refsum Disease:
Case Report of Two Family Members
Dubois et al.
American Journal of Neuroradiology
12:1159-1160, November/December 1991

Treatment of infantile phytanic acid storage disease:
clinical, biochemical and ultrastructural findings in
two children treated for 2 years
Robertson et al.
European Journal of Pediatrics, 147:133-142, 1988

Infantile Refsum's disease; a generalized peroxisomal disorder:
Case report with postmortem examination
Torvik et al.
Journal of Neurological Sciences, 85:39-53, 1988

Infantile Refsum disease: an inherited peroxisomal disorder
Comparison with Zellweger syndrome and neonatal adrenoleukodystrophy
Poll-The et al.
European Journal of Pediatrics, 146: 477-483, 1987

Impaired plasmalogen metabolism in infantile Refsum's disease
Poll-The et al.
European Journal of Pediatrics, 144: 513-514, 1986

Dysmorphic syndrome with phytanic acid oxidase deficiency,
abnormal very long chain fatty acids and pipecolic acidemia:
Studies in four children
Budden, Kennaway, Buist, Poulos, Weleber
The Journal of Pediatrics
Vol. 108, No. 1, 33-39, January 1986

A milder variant of Zellweger syndrome
Barth et al.
European Journal of Pediatrics, 144: 338-342, 1985

Absence of hepatic peroxisomes in a case of
infantile Refsum's disease
Ogier et al.
Scandanavian Journal of Clinical Lab Investigation
45:767-768, 1985

Patterns of Refsum's disease
Poulos et al.
Archives of Disease in Childhood, 59:222-229, 1984
 
Infantile Refsum's disease (phytanic acid storage disease):
a variant of Zellweger's syndrome?
Poulos et al.
Clinical Genetics, 26:79-586, 1984
 
Plasma and skin fibroblast C26 fatty acids in
infantile Refsum's disease
Poulos and Sharp
Neurology, 34:606-1609, 1984

Ophthalmic Manifestations of Infantile
Phytanic Acid Storage Disease
Weleber, Tongue, Kennaway, Budden, Buist
Archives of Ophthalmology, 102:1317-1321, September 1984

Infantile Phytanic Acid Storage Disease, a possible
Variant of Refsum's disease: Three Cases, including
Ultrastructural Studies of the Liver
Scotto et al.
Journal of Inherited Metabolic Disease, 5:83-90, 1982
 
Infantile Phytanic Acid Storage Disease:
A Variant of Refsum's Disease?
Boltshauser et al.
19th Workshop for Pediatric Research,
European Journal of Pediatrics, 139:317, 1982

[Return to Index]

- - -

Rhizomelic Chondrodysplasia Punctata (RCDP type 1)
[McKusick No. 215100]

Rhizomelic chondrodysplasia punctata is a peroxisomal
protein targeting disease caused by a non-functional
PTS2 receptor
Motley et al.
Nature Genetics 15:377-380, April 1997

Non-rhizomelic and rhizomelic chondrodysplasia punctata
within a single complementation group
Motley et al.
Biochimica et Biophysica Acta
Vol 1315, No. 1, 153-158, January 1996

Rhizomelic Chondrodysplasia Punctata: Report of a Case
with Review of the Literature and Correlation with Other
Peroxisomal Disorders
Agamanolis and Novak
Pediatric Patholgy & Laboratory Medicine, 15: 503-513, 1995

Multiple peroxisomal enzyme deficiencies in rhizomelic
chondrodysplasia punctata: comparison with Zellweger syndrome,
Conradi-Hunermann syndrome and the X-linked dominant type of
chondrodysplasia punctata
Schutgens et al.
Advances in Clinical Enzymology, 6:57, 1988

Chondrodysplasia Punctata - Rhizomelic Form
Pathologic and Radiologic Studies of Three Infants
Gilbert et al.
European Journal of Pediatrics, 123:89-109, 1976

(PTS2 receptor)  PEX7  [McKusick No.601757]

WIS GeneCard :
PEX7      http://bioinformatics.btk.utu.fi/genecards/cgi-bin/carddisp?PEX7
 
 [Return to Index]

- - -

Pipecolic Acidemia [McKusick No. 239400]

Hyperpipecolic acidemia associated with hepatomegaly,
mental retardation, optic nerve dysplasia, and progressive
neurologic disease
Thomas et al.
Clinical Genetics, 8: 376, 1975

Hyperpipecolatemia: a new metabolic disorder associated
with neuropathy and hepatomegaly: a case study
Gatfield et al.
Journal of the Canadian Medical Association
99:1215-1233, 1968

[Return to Index]

- - -

Others, not readily classified:

Biochemical Features of a Patient with Zellweger-like Syndrome
with Normal PTS-1 and PTS-2 Peroxisomal Protein Import Systems
Singh et al.
Biochemical and Molecular Medicine, 61, 198-207, 1997

Pseudo Infantile Refsum's Disease: Catalase-Deficient Peroxisomal
Particles with Partial Deficiency of Plasmologen Synthesis and
Oxidation of Fatty Acids
Aubourg et al.
Pediatric Research,Vol 34, No. 3, September, 1993

[Return to Index]

PEROXISOMAL SINGLE ENZYME DISORDERS

Fatty Acid beta-Oxidation:

X-linked Adrenoleukodystrophy (X-ALD); Adrenomyeloneuropathy (AMN)
(ATP-binding transport [ALDP] deficiency} [McKusick No. 300100]

Adrenoleukodystrophy: phenotype, genetics,
pathogenesis, and therapy
Moser
Brain, 120:1485-1508, 1997

X-linked adrenoleukodystrophy: clinical presentation,
diagnosis, and therapy
Van Geel et al.
Journal of Neurology, Neurosurgery, and Psychiatry
63:4-14, 1997

Adrenoleukodystrophy: molecular genetics, pathology,
and Lorenzo's oil
Moser, Powers, Smith
Brain Pathology, 5:259-266, 1995

[Return to Index]

- - -
Pseudo-Zellweger syndrome    [McKusick No. 261510]
(3-oxoacyl-CoA [thiolase] deficiency)

Reinvestigation of Peroxisomal 3-Ketoacyl-CoA Thiolase
Deficiency: Identification of the True Defect at the Level of
D-Bifunctional Protein
Ferdinandusse et al.
American Journal of Human Genetics
70:1589-1593, 2002

Bile Acid Profiles in Peroxisomal 3-Oxoacyl-Coenzyme A
Thiolase Deficiency
Clayton et al.
Journal of Clinical Investigation
Vol. 85, 1267-1273, April 1990

Human peroxisomal 3-oxoacyl-Coenzyme A thiolase deficiency
Schram et al.
Proceeds of the National Academy of Sciences (USA)
84:2494-2496, 1987

Pseudo-Zellweger syndrome: deficiencies in several
peroxisomal oxidation activities
Goldfischer et al.
Journal of Pediatrics, 108:25-32, 1986
 
WIS GeneCard:
( Peroxisomal 3-oxoacyl CoA thiolase =) acetyl-CoA acylransferase ACAA1
http://bioinfo.weizmann.ac.il/cards-bin/carddisp?ACAA1

ExPASy
http://www.expasy.ch/cgi-bin/get-enzyme-entry?2.3.1.16

[Return to Index]

- - -
Pseudo-NALD [McKusick No. 264470]
(Acyl-CoA oxidase [AOx] deficiency)

Large deletion of the peroxisomal acyl-CoA oxidase gene
in pseudo-neonatal adrenoleukodystrophy
Fournier et al.
Journal of Clinical Investigation
94:526-531, 1994

A new peroxisomal disorder with enlarged peroxisomes and
a specific deficiency of Acyl-CoA oxidase
(pseudo-neonatal adrenoleukodystrophy)
Poll-The et al.
American Journal of Human Disease, 42:422-434, 1988
 

[Return to Index]

- - -
Pseudo-NALD [McKusick No. 261515]
(Bifunctional enzyme [BIF] deficiency)
(CoA hydratase/3-hydroxyacyl-CoA dehydrogenase)

Distinction Between Peroxisomal Bifunctional Enzyme
and Acyl-CoA Oxidase Deficiencies
Watkins et al.
Annals of Neurology, Vol. 38, No. 3, 472-477
September 1995

Bifunctional enzyme deficiency - identification of a new
type of peroxisomal disorder in a patient with an impairment
in peroxisomal beta-oxidation, etc.
Wanders et al.
Journal of Inherited Metabolic Disease
15:385-388, 1992

Peroxisomal bifunctional enzyme deficiency
Watkins et al.
Journal of Clinical Investigation
83:771-777, 1989

[Return to Index]

- - -
Other Peroxisomal beta-Oxidation Defects
{i.e. not attributed to thiolase, AOx, or
BIF deficiencies):

Neonatal Seizures and Severe Hypotonia in a Male
Infant Suffering from a Defect in Peroxisomal
beta-Oxidation
van Maldergem et al.
Neuromuscular Disorders, Vol. 2, No. 3, 217-224, 1992

Peroxisomal beta-oxidation defect with detectable
peroxisomes: a case with neonatal onset and
progressive course
Barth et al.
European Journal of Pediatrics, 149:722-726, 1990

Neonatal seizures and retardation in a female with
biochemical features of X-linked adrenoleukodystrophy
Naidu et al.
Neurology, 38:1100-1007, 1988

[Return to Index]

- - -

Ether-phospholipid (including plasmalogen) synthesis:

DHAP-AT deficiency
(RCDP type 2, formerly pseudo-RCDP) [McKusick No. 222765]

Rhizomelic chondrodysplasia punctata type 2 (RCDP2) is a disorder resulting from a deficiency of the protein dihydroxyacetonephosphate acyltransferase DHAP-AT (also known as glyceronephosphate O-acyltransferase GNPAT). DHAP-AT is a peroxisomal enzyme necessary to the inital step in the synthesis of ether-phopholipids from which, in turn, plasmalogens are derived. (The specific reaction is that of incorporating an acyl group {i.e. fatty acid chain} at the sn-1 position of dihydroxyacetone phosphate, resulting in 1-acyldihydroxyacetone phosphate. See Harper's Chapter 26, and figure 26-4)

The name RCDP2 derives from observed clinical similarities between this disorder and RCDP1: dwarfism characterized by abnormal shortening of the upper limbs, abnormalities of bone and cartilage, facial dysmorphia, hypotonia, epileptic seizures, developmental delay, cataracts, and abnormal myelination of the brain and central nervous system. However, RCDP1 is a peroxisome biogenesis disorder attributable to mutations of the PEX7 gene, which codes for the PTS-2 receptor, with resulting failure or deficiency in the import of all PTS2 proteins into the peroxisome: DHAP-AT and alkyl-DHAP synthase, involved in the synthesis of ether-phospholipids; phytanoyl-CoA hydroxylase, involved in the metabolism of phytanic acid; and an abnormality of 3-ketoacyl-CoA thiolase, involved in the beta-oxidation of fatty acids. RCDP2 results only from mutation of the gene colding for DHAP-AT, and the subsequent deficiency in the synthesis of ether-phospholids is the only biochemical abnormality.

(There appears to be evidence that DHAP-AT in fact has a PTS1 targeting signal. It is not understood why children with RCDP1, which affects the import of PTS2 proteins into the peroxiosme, also then display the DHAP-AT deficiency. See Ofman et al., 1998, below).

RCDP2 is described in only a dozen or so cases, and there are variations within it, both in the exitence and/or severity of the associated clinical signs. For example, there are cases of RCDP2 in which there is no rhizomelia, or in which the develpmental delays are less severe, etc.

Acyl-CoA:dihydroxyacetonephosphate acyltransferase:
cloning of the human cDNA and resolution of the molecular
basis in rhizomelic chondrodysplasia punctata type 2
Ofman et al.
Human Molecular Genetics
Vol. 7, No. 5, 847-853, 1998

Abnormal Myelination in Peroxisomal Isolated DHAP-AT deficiency
Sztriha et al.
Pediatric Neurology, Vol 16, No. 3, 232-236, April 1997

Isolated dihydroxyacetonephophate acyltransferase deficiency
presenting with developmental delay
Clayton et al.
Journal of Inherited Metabolic Disease
17:533-540, 1994

Rhizomelic chondrodysplasia punctata with
isolated DHAP-AT deficiency
Barr et al.
Archives of the Diseases of Childhood
Vol. 68, No. 3, 415-417, March 1993

Human dihydroxyacetonephosphate acyltransferase deficiency:
a new peroxisomal disorder
Wanders et al.
Journal of Inherited Metabolic Disease
15:389-391, 1992

WIS GeneCard:
{DHAP-AT =) glyceronephospahate O-acyltransferase GNPAT
http://bioinfo.weizmann.ac.il/cards-bin/carddisp?GNPAT
 
DHAP-AT ; GNPAT [McKusick No. 602744]

[Return to Index]

- - -
Alkyl-DHAP synthase deficiency
(RCDP type 3, formerly also pseudo-RCDP) [McKusick No. 600121]

Rhizomelic chondrodysplasia punctata type 3 (RCDP3) is a disorder resulting from a deficiency of the protein alkydihydroxyacetonephosphate synthase (alkyl-DHAP synthase; also known as alkyglycerone phosphate synthase AGPS). Alkyl-DHAP synthase is a peroxisomal enzyme necessary to the second step in the biosynthesis of ether phospholipids, which are, in turn, the precursors of plasmalogens. (The specific reaction is the substitution of a long-chain alcohol for the acyl group at the sn-1 position of 1-acyldihydroxyacetone phosphate, resulting in 1-alkyldihydroxyacetone phosphate. See Harper's Chapter 26 and figure 26-4).

As with RCDP2, RCDP3 takes its name from early observations of its clinical similarity to RCDP1. However, it is the result of just the one deficient protein and not the entire range of PTS2 proteins as in RCDP1. In RCDP3, as in RCDP2, the defective synthesis of ether phospholipids is the only biochemical abnormality. RCDP3 is described in only a very few - possibly just two or three - cases.

Prenatal diagnosis of rhizomelic chondrodysplasia punctata due
to isolated alkyldihydroxyacetonephosphate synthase deficiency
Brookhyser et al.
Prenatal Diagnosis, 19:383-385, 1999

Alkyl-dihydroxyacetonephosphate synthase: fate in peroxisome
biogenesis disorders and identification of the point mutation
underlying a single enzyme deficiency
de Vet et al.
Journal of Biological Chemistry, 273:10296-10301, 1998

Human alkyldihydroxyacetonephosphate synthase deficiency:
a new peroxisomal disorder
Wanders et al.
Journal of Inherited Metabolic Disease
17:315-318, 1994

WIS GeneCard:
(alkyldihydroxyacetonephosphate synthase =)
alkylglcerone phosphate synthase AGPS
http://bioinfo.weizmann.ac.il/cards-bin/carddisp?AGPS
 
AGPS  [McKusick No.603051]

[Return to Index]

- - -
Other single-enzyme disorders:

Glutaric aciduria type 3
(Glutaryl-CoA oxidase deficiency) [McKusick No. 231690]

Atypical riboflavin-responsive glutaric aciduria
and deficient peroxisomal glutaryl-CoA oxidase
activity: a new peroxisomal disorder
Bennett et al.
Journal of Inherited Metabolic Disease
14:165-173, 1991

[Return to Index]

- - -
Mevalonic aciduria
(Mevalonate kinase deficiency)

Differential Deficiency of Mevalonate Kinase and
Phosphomevalonate Kinase in Patients with Distinct
Defects in Peroxisome Biogenesis
Wanders and Romeijn
Biochemical and Biophysical Research Communications
Vol 247, No. 3, 663-667, 1998

Clinical and biochemical phenotype in 11 patients
with mevalonic aciduria
Hoffmann et al.
Pediatrics, 91:915-921, 1993

Molecular cloning of human mevalonate kinase and
identification of of a missense mutation in the
in the genetic disease mevalonic aciduria
Schafer et al.
Journal of Biological Chemistry
267:13229-13238, 1992

[Return to Index]

- - -
Primary hyperoxaluria type 1 (PH1) [McKusick No. 259900]
(Peroxisomal alanine:glyoxylate aminotransferase [AGT] deficiency)

Recent advances in the understanding, diagnosis and
treatment of primary hyperoxaluria type 1
Danpure
Journal of Inherited Metabolic Disease
12:210-224, 1989

Peroxisomal alanine:glyoxylate aminotransferase
deficiency in primary hyperoxaluria type 1
Danpure and Jennings
FEBS Letter, 201:20-24, 1986

[Return to Index]

- - -
Acatalasemia [McKusick No. 115500]
(Peroxisomal catalase deficiency)

Molecular defect in human acatalasia fibroblasts
Crawford et al.
Biochemical and Biophysical Research Communications
Vol. 153, No. 1, 59-66, 1988

WIS GeneCard:
Peroxisomal catalase (CAT)
http://bioinfo.weizmann.ac.il/cards-bin/carddisp?CAT

[Return to Index]

- - -
Refsum disease; Adult Refsum disease;
Phytanic acid storage disease [McKusick No. 266500]
(Phytanoyl-CoA hydroxylase deficiency)

Refsum Disease: A Defect in the alpha-Oxidation of
Phytanic Acid in Peroxisomes
Singh et al.
Journal of Lipid Research, 34:1755-1764, 1993

Heredopathia Atactica Polyneuriformis
Sigvald Refsum
Archives of Neurology, 38:605-606, October 1981

a-Oxidation of branched chain fatty acids in man and its
failure in patients with Refsum disease showing phytanic
acid accumulation
Evrard, Stokke, Try
Scandanavian Journal of Clinical Lab Investigation
18:694-695, October 1966

WIS GeneCard:
Phytanoyl-CoA hydroxylase (PHYH)
http://bioinfo.weizmann.ac.il/cards-bin/carddisp?PHYH

PHYH [McKusick No. 602026]

[Return to Index]

N-3 and N-6 FATTY ACIDS

General

Essential fatty acids in early life:
structural and functional role
Uauy, Mena, Rojas
Proceedings of the Nutrition Society
59:3-15, 2000

Plasma and Red Blood Cell Fatty Acids
in Peroxisomal Disorders
Moser, Jones, Raymond, Moser
Neurochemical Research
Vol. 24, No. 2, 187-197, 1999

Polyunsaturated fatty acid biosynthesis:
a microsomal-peroxisomal process
Sprecher and Chen
Prostaglandins, Leukotrienes and Essential Fatty Acids
Vol. 60, No. 5&6, 317-321, 1999

Recent Advances in the Biology
of n-6 Fatty Acids
Galli and Marangoni
Nutrition, Vol 13, Nos. 11/12, 1997

Maninpulation of the fate of long chain
polyunsaturated fatty acids in cultured cells
Galli et al.
Prostaglandins, Leukotrienes,& Essential Fatty Acids
Vol 57, No. 1, 23-26, 1997

Omega-3 fatty acids and the peroxisome
Colin Masters
Molecular and Cellular Biochemistry
165:83-93, 1996

Reevaluation of the pathways for the biosynthesis
of polyunsaturated fatty acids
Sprecher et al.
Journal of Lipid Research, 36:2471-2477, 1995

New Biological and Clinical Roles for
the N-6 and N-3 Fatty Acids
Harald Hansen
Nutrition Reviews
Vol 52, No. 5, 162-167, May 1994

[Return to Index]

- - -
Docosahexaenoic Acid

Brain Uptake and Utilization of Fatty Acids:
Applications to Peroxisomal Biogenesis Disorders
(The Roles of DHA in Zellweger Syndrome,
a Representitive Peroxisomal Biogenesis Disorder)
Discussion, various participants
Journal of Molecular Neuroscience, 16:317-321, 2001

Regulation of the Biosynthesis of
4,7,10,13,16,19-Docosahexaenoic Acid
Luthria et al.
Journal of Biological Chemistry
Vol. 271, No. 27, 16020-16025, July 1996

Peroxisomes in Mice Fed a Diet Supplemented
with Low Doses of Fish Oil
Van den Branden et al.
Lipids, Vol 30, No. 8, 701-705, 1995

The Accretion of Docosahexaenoic Acid in the Retina
Anderson et al.
(in) Fatty Acids and Lipids: Biolgical Aspects
Galli et al. (editors)
World Review of Nutrition and Dietetics
Vol. 75, 124-127, 1994

Restoring the DHA Levels in the Brains of
Patients with Zellweger Syndrome
Martinez
Journal of Molecular Neuroscience, 16:309-316, 2001

Blood Polyunsaturated Fatty Acids in
Patients with Peroxisomal Disorders
Martinez et al.
Lipids, Vol.29, No. 4, 1994

Docosahexaenoic acid - a new therapeutic
approach to peroxisomal-disorder patients:
Experience with two cases
Martinez et al.
Neurology, 43: 1389-1397, July, 1993

Abnormal profiles of polyunsaturated fatty acids
in the brain, liver, kidney and retina of patients
with peroxisomal disorders
Martinez
Brain Research, 583: 171-182, 1992

Tissue levels of polyunsaturated fatty acids
during early human development
Martinez
The Journal of Pediatrics, 120:S129-S138, April 1992

Severe deficiency of docosahexaenoic acid
in peroxisomal disorders
Martinez
Neurology, 40:1292-1298, 1990
 
[Return to Index]

- - -
Arachidonic Acid and the Eicosanoids

The Biochemistry of Prostaglandins
O'Neill
The Australian and New Zealand Journal
of Obstetrics & Gynaecology,
Vol 34, No. 3, 332-337, 1994
 
The role of eicosanoids in paediatrics
Seyberth and Kuhl
European Journal of Pediatrics
Vol. 147, No.4, 341-349, 1988
 
[Return to Index]

OTOLOGY

Infantile Refsum's Disease; a generalized peroxisomal disorder
Case Report with postmortem examination
Torvik et al.
Journal of the Neurological Sciences (Elsevier) 85: 39-53 (1988)

Cochlear nerve degeneration coincident with adrenocerebroleukodystrophy
Igarashi et al.
Archives of Otolaryngology 102: 722-726, December 1976

[Return to Index]

OPHTHALMOLOGY

Genetic Diseases of the Eye
(Traboulsi, editor) Oxford University Press, 1998
Chapter 33, Peroxisomal Disorders
Richard Weleber

The Peroxisome and the Eye
Folz and Trobe
Survey of Ophthalmolgy, Vol. 35, No 5, 353-368
March-April 1981

Ocular Histopathologic and Biochemical Studies of the
Cerebrohepatorenal Syndrome (Zellweger's Symdrome) and its
Relation to Neonatal Adrenoleukodystrophy
Cohen et al.
American Journal of Ophthalmology, 96:488-501, 1983

Tapetoretinal degeneration in the cerbro-hepato-renal
(Zellweger's) syndrome
Garner et al.
British Journal of Ophthalmology, 66, 421-431, 1982

Ocular Manifestations of Conradi and Zellweger Syndromes
Kretzer et al.
Metabolic and Pediatric Ophthalmology
Vol. 5, 1-11, 1981

Zellweger Syndrome: Lenticular Opacities Indicating
Carrier Status and Lens Abnormalities Characteristic
of Homozygotes
Hittner et al.
Archives of Ophthalmology
Vol. 99, 1977-1982, November 1981

Cerebro-hepato-renal Syndrome of Zellweger:
Ocular Histopathologic Findings
Haddad et al.
Archives of Ophthalmology
Vol. 94, 1927-1930, November 1976

Cerebro-hepato-renal (Zellweger's) Syndrome:
Ocular Involvement
Stanescu and Dralands
Archives of Ophthalmology
Vol. 87, 590-592, May 1972

A syndrome of ocular abnormalities, calcification of cartilage,
and failure to thrive
Punnett and Kirkpatrick
Journal of Pediatrics
Vol. 73, No. 4, 602-606, Ocotber 1968

Ocular Histopathologic Studies of Neonatal
and Childhood Adrenoleukodystrophy
Cohen et al.
American Journal of Ophthalmology, 95:82-96, 1983

Ocular Pathologic Findings in Neonatal Adrenoleukodystrophy
Glasgow et al.
Ophthalmology, Vol 94, No. 8, 1054-1060, August 1987

Ophthalmic Manifestations of Infantile Phytanic Acid
Storage Disease
Weleber et al.
Archives of Ophthalmology, Vol. 102, 1317-1321
September 1984

Hyperpipecolic acidemia associated with hepatomegaly,
mental retardation, optic nerve dysplasia and
progressive neurological disease
Thomas et al.
Clinical Genetics, 8:376-382, 1975

Ocular Involvement in Chondrodysplasia Punctata
Levine et al.
American Journal of Ophthalmology
Vol. 77, No. 6, 851-859, June 1974

Dysplasia epiphysialis punctata with ocular anomalies
Hammond
British Journal of Ophthalmology, 54, 755-758, 1970

Peroxisome bifunctional enzyme deficiency with
associated retinal findings
Al-Hazza and Ozand
Ophthalmic Genetics, Vol 18, No. 2, 93-99, 1997

Ocular Findings in Primary Hyperoxaluria
Small et al.
Archives of Ophthalmology
Vol. 108, 89-93, January 1990

Optic Atrophy in Primary Oxalosis
Small et al.
American Journal of Ophthalmology
Vol. 106, No. 1, July 1988

Ocular Involvement in Primary Hyperoxaluria
Meredith et al.
Archives of Ophthalmology
Vol. 102, 584-587, April 1984

Ophthalmic manifestations of primary oxalosis
Fielder et al.
British Journal of Ophthalmology, 64, 782-788, 1980

"Flecked retina" - an association with
primary hyperoxaluria
Gottlieb et al.
Journal of Pediatrics
Vol. 90, No. 6, 939-942, June 1977

Heredopathia Atactica Polyneuritiformis:
Phytanic-Acid Storage Disease, Refsum's Disease:
A Biochemically Well-defined disease with a
Specific Dietary Treatment
Sigvald Refsum
Archives of Neurology
Vol. 38, 605-606, October 1981

Brainstem Auditory, Visual and Somatosensory
Evoked Potentials in Leukodystrophies
Markand et al.
Electroencephalography and Clinical Neurophysiology
54:39-48, 1982

Correlation of phenotype with genotype
in inherited retinal degeneration
Daiger et al.
Behavioral and Brain Sciences, 18:452-467, 1995

The Inherited Neurodegenerative Diseases of Childhood:
Clinical Assessment
Percy
Journal of Child Neurology
Vol. 2, 82-97, April 1987

The retinal pigment epithelium:
a versatile partner in vision
Dean Bok
Journal of Cell Science, Supplement 17, 189-195, 1993

Localization of Nonspecific Lipid Transfer Protein
(nsLPT = Sterol Carrier Protien 2) and Acyl-CoA Oxidase
in Peroxisomes of Pigment Epithelial Cells of Rat Retina
Deguchi et al.
Journal of Histochemistry and Cytochemistry
Vol. 40, No. 3, 403-410, 1992

Peroxisomes in Pigment Epithelium and Muller Cells of
Amphibian Retina Possess d-Amino Acid Oxidase
as well as Catalase
Beard et al.
Experimental Eye Research, 47, 343-348, 1988

Microperoxisomes in Retinal Epithelium and
Tapetum Lucidum of the American Opossum
Hazlett et al.
Experimental Eye Research, 27, 343-348, 1978

Studies on Microperoxisomes:
VII. Pigment Epithelial Cells and
Other Cell Types in the Retina of Rodents
Leuenberger and Novikoff
Journal of Cell Biology
Vol. 65, 324-334, 1975

Microperoxisomes in retinal pigment epithelium
Robison and Kuwabara
Ivestigative Ophthalmology
Vol. 14, No. 11, 866-872, November 1975

The dolichol pathway in the retina and its involvement
in the glycolysation of rhodopsin
Edward Kean
Biochimica et Biophysica Acta
1473:272-285, 1999

[Return to Index]

DIET AND NUTRITION
 
Pediatric Nutrition in Chronic Diseases
and Developmental Disorders
Oxford University Press, New York, 1993
Chapter 47 - Adrenoleukodystrophy and Related
Peroxisomal Disorders
Janet Borel

A randomized controlled trial of early dietary
supply of long-chain polyunsaturated fatty acids
and mental development in term infants
Birch et al.
Developmental Medicine and Child Neurology
42:174-181, 2000

[Return to Index]

PEROXISOME PROLIFERATORS

Pharmacological Induction of Peroxisomes in
Peroxisome Biogenesis Disorders
Wei et al.
Annals of Neurology, 47:286-296, 2000

VITAMIN K

The Molecular Basis of Blood Coagulation
Furie and Furie
Cell, 53:505-518, 20 May 1988

A Comprehensive Review of Vitamin K and
Vitamin K Antagonists
Vermeer and Schurgers
Journal of the Hematology/Oncology Clinics of North America
Vol. 14, No. 2, April 2000

Vitamin K-Dependent Proteins
Nelsestuen et al.
Vitamins and Hormones
Vol. 58, 355-387, 2000

The Vitamin K-dependent Proteins: An Update
Guylaine Ferland
Nutrition Reviews
Vol. 56, No. 8, 223-230, August 1998

Vitamin K and Tissue Mineralization
Vermeer et al.
Bibl Nutr Dieta, No. 55, 159-170, 2001

Role of Vitamin K in Bone Metabolism
Vermeer et al.
Annual Review of Nutrition, 15:1-22, 1995

Vitamin K-dependent Proteins in the
Developing and Aging Nervous System
Katherine Tsaioun
Nutrition Reviews
Vol. 57, No. 8, 231-240, August 1999

Heriditary Deficiency of Vitamin K-Dependent
Coagulation Factors with Skeletal Abnormalities
Boneh and Bar-Ziv
American Journal of Medical Genetics
65:241-243, 1996

Linus Pauling Institute, Oregon State Unversity
http://www.orst.edu/dept/lpi/infocenter/vitamins/vitaminK/k.html

Coag Factor II  (prothrombin) [McKusick No. 176930]
WIS GeneCard http://bioinfo.weizmann.ac.il/cards-bin/carddisp?F2&search=prothrombin&suff=txt

[Return to Index]

- - - - - - -
GENERAL TEXTS
 
(Edition numbers and publication dates are not given; the most
recent versions available should of course always be used.)

The Metabolic and Molecular Basis of Inherited Disease
McGraw-Hill Book Company, New York
 
Taber's Cyclopedic Medical Dictionary
F. A. Davis Company, Philadelphia
 
Harper's Biochemistry
Murray, Granner, Mayes, Rodwell
(Lange Medical Books)
Appleton & Lange, Norwalk, Connecticut

Biochemistry
Lubert Stryter (Stanford University)
W. H. Freeman and Company, San Fransisco
 
Molecular Cell Biology
Lodish, Berk, Zipursky, Matsudaira, Baltimore, Darnell
Scientific American Books
(distributed by W. H. Freeman and Company, New York)
 
Molecular Biology of the Cell
Alberts, Bray, Lewis, Raff, Roberts, Wilson
Garland Publishing
(Taylor & Francis Group, New York)

Essential Cell Biology
Widnell and Pfenninger
Williams & Wilkins, Baltimore

Cell and Molecular Biology
De Robertis and De Robertis
Lea & Febiger, Philadelphia

Basic Neurochemistry
Siegel, Agranoff, Albers, Molinoff
Raven Press, New York

[Return to Index]


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