Peroxisome Biogenesis Disorder 3A and 3B (PEX12)

Peroxisome biogenesis disorder 3A and 3B are autosomal recessive disorders caused by pathogenic variants in the gene PEX12.

  • Peroxisome biogenesis disorder 3A is a form of Zellweger syndrome characterized by craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctate. Affected individuals present with profound hypotonia, seizures, and inability to feed in the neonatal stage. Life expectancy of the affected individuals is extremely low and most individuals die within the first year of life.
  • Peroxisome biogenesis disorder 3B comprises neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger syndrome spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood.

A genotype-phenotype relationship has been reported, in that patients with two null variants exhibit a more severe phenotype.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):