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Peroxisome biogenesis disorder

Synonym(s) Peroxisome biogenesis disorder spectrum
Prevalence Unknown
Inheritance Autosomal recessive
Age of onset Infancy
ICD-10 -
  • C1832200
  • C536664
MedDRA -


Disease definition

Peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD-ZSS) is a group of autosomal recessive disorders affecting the formation of functional peroxisomes, characterized by sensorineural hearing loss, pigmentary retinal degeneration, multiple organ dysfunction and psychomotor impairment, and is comprised of the phenotypic variants Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) (see these terms).


The estimated incidence for PBD-ZSS is 1/50,000 births in the United States and 1/500,000 births in Japan.

Clinical description

The term PBD-ZSS reflects the disease spectrum seen in the severe, mild and intermediate variants that were described before their peroxisome etiology was known. The three subtypes have overlapping clinical phenotypes of varying degrees of severity, with ZS being the most, and IRD the least severe. Their distinction is not always clear in individual cases as patients with NALD and IRD display phenotypes that often overlap while ZS patients tend to have a more uniform presentation. Onset of manifestations is usually soon after birth or in childhood and includes neonatal seizures, hypotonia, distinctive craniofacial features (flattened facies, broad nasal bridge, widely split sutures, large anterior fontanelle), liver dysfunction, and in older children progressive sensorineural hearing loss, retinal dystrophy and developmental delays. Additional complications that can develop include adrenal insufficiency, calcium oxalate renal stones and episodes of hemorrhage and intracranial bleeding, the latter secondary to liver dysfunction and coagulopathy. The craniofacial features are most prominent in ZS, although they can still be recognizable in NALD and IRD. Atypical presentations of PBD-ZSS have recently been recognized.


The mutations found in 90% of PBD-ZSS patients are in the PEX1, PEX6, PEX10, PEX12 or PEX26 genes. Genetic defects in the PEX1 gene (seen in approximately 70% of cases), and subsequent alteration of the metabolic function of the peroxisome organelle is the most common cause of PBD-ZSS. The other less common disease causing mutations are found in the PEX13, PEX14, PEX16, PEX19, PEX2, PEX3, PEX5, and PEX11B genes. Two PEX genes, PEX11G and PEX11A remain thus far unassociated with disease. Impaired metabolism results in the accumulation of very-long-chain fatty acids (VLCFAs), which damage developing neural cells. Accumulation of toxic bile acid intermediates damages the liver. The decreased synthesis of docosahexanoic acid (DHA) and ether phospholipids (plasmalogens) impairs cell membranes. In the 13 PEX genes associated with PBD-ZSS, there are no correlations between disease severity and the causative PEX gene. Rather, there is a general correlation between the predicted effects of the PEX gene mutation on the function of the encoded PEX protein (peroxin). Thus, mutations that encode nonfunctional peroxins are associated with ZS, and mutations that encode peroxins with residual functions are associated with less severe phenotypes.

Expert reviewer(s)

  • Dr Nancy BRAVERMAN

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Guidance for genetic testing
Article for general public
Clinical genetics review
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