Peroxisome Biogenesis Disorder 11b

A number sign (#) is used with this entry because this form of peroxisome biogenesis disorder (PBD11B) is caused by homozygous mutation in the PEX13 gene (601789) on chromosome 2p15.

Mutations in the PEX13 gene also cause Zellweger syndrome (PBD11A; 614883).

Description

The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. 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 (summary by Waterham and Ebberink, 2012).

For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539.

Individuals with mutations in the PEX13 gene have cells of complementation group 13 (CG13, equivalent to CGH). For information on the history of PBD complementation groups, see 214100.

Clinical Features

Shimozawa et al. (1998) described a patient with a peroxisome biogenesis disorder who was the child of nonconsanguineous Caucasian parents. Pregnancy, birth, and milestones during the first postnatal year were normal. After an upper respiratory infection at the age of 16 months he became ill with rapidly progressive hypotonia and muscle weakness leading to severe generalized paresis within 2 months, and gavage feeding became necessary. Loss of hearing and visual decline followed within 6 months of onset. There was no external dysmorphia or hepatosplenomegaly. The patient was given a diagnosis of NALD.

Krause et al. (2006) reported a Turkish girl with a progressive clinical course characterized by hypotonia and cataracts. She had caudal neuropore and inverted nipples, but none of the dysmorphic features seen in classic Zellweger syndrome. She died at 31 months of age.

Molecular Genetics

Liu et al. (1999) identified homozygosity for a missense mutation in the PEX13 gene (I326T; 601789.0002) in the patient with NALD described by Shimozawa et al. (1998).

In a Turkish girl with a peroxisome biogenesis disorder, Krause et al. (2006) identified homozygosity for a missense mutation in the PEX13 gene (W313G; 601789.0005).