Peroxisome Disorders

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Contents


See also these assocated articles:


Classification

Modern consensus is for two classification groups based on peroxisome structure / defiency. Previous classification was based on clinical criteria.

  1. Peroxisome Biogenesis Disorders (PBDs): abnormal and defective peroxisomes
    1. mututations are within the Peroxin Protein Genes (PEX genes)
  2. Single enzyme deficiencies (intact peroxisome structure)


  1. Peroxisome Biogenesis Disorders (PBDs): abnormal and defective peroxisomes
    1. Zellweger's Syndrome
    2. Infantile Refsum's Disease
    3. Adrenoleukodystrophy
    4. Hyperpipecolic Academia (HPA)
    5. Rhizomelic chondrodysplasia punctata type I


  1. Single enzyme deficiencies
    1. Disorders of peroxisomal beta-oxidation (POD), eg:
      1. X-linked adrenoleukodystrophy (X-ALD)
      2. Adrenomyeloneuropathy (AMN)- a variant of X-ALD
    2. Disorders of ether-phospholipid biosynthesis
      1. eg. rhizomelic chondrodysplasia punctata (RCDP) types I, II, III
    3. Disorders of fatty acid alpha-oxidation
      1. Refsum's Disease (accumulation of phytanic acid)


Incidence

  • Combined incidence: 1:20 000


What are peroxisomes?

Peroxisomes are organelles within eukaryotic cells. Contained by a lipid bi-layer membrane, they are involved in the metabolism of fatty acids, biosynthesis of cholesterol, production of ether phospholipids (eg. plasmalogen and platelet activating factor, PAF) and synthesis of bile acid. They also detoxify various cellular metabolites, including peroxides.


Mitochondria are responsible for the oxidation of most fatty acids. However, Peroxisomes are essential for beta-oxidation of very-long-chain fatty acids (VLCFAs).


Accumulation of VLCFAs is pathognomonic of a Peroxisomal disorder, for example Zellweger's Syndrome.


Disease Pathogenesis

VLCFA accumulation is damaging to white matter in the CNS leading to inflammation and demyelination.


CNS migration defects are also common with peroxisomal disorders, and are thought to be the main cause of intractable seizures and severe psychomotor retardation. Plasmalogen and PAF are thought to be important for cell membrane integrity and signalling, particularly within the CNS, respectively.


VLCFA accumulation can also cause an Addisonian-like phenotype; adrenal cells are seen to response poorly to ACTH.


Prognosis and Clinical Features

  • Zellweger's Syndrome - severe: apparent at birth, death within first year.
  • Childhood adrenoleukodystrophy - total disability during first 10 years of life; death thereafter
  • Refsum's Disease (accumulation of phytanic acid)
  • Other patients: may live 10-20 years.


Zellweger's Syndrome is the most severe form (view the article for a full description of clinical features). Other phenotypes are usually milder, although sensorineural hearing loss and pigmentary retinal degeneration is invariably present. Neuronal migration defects are much less common and seizures absent. Leukodystropy may be present. Stature is short and tooth eruption delayed. Renal cysts and stippling of the epiphyses (chondroplasia punctata) are not present.


References

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