Peroxisome Biogenesis Disorder 5a (Zellweger)

A number sign (#) is used with this entry because this form of Zellweger syndrome (PBD5A) is caused by homozygous mutation in the PEX2 gene (170993) on chromosome 8q21.

Description

The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006).

For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100.

Individuals with PBDs of complementation group 5 (CG5, equivalent to CG10 and CGF) have mutations in the PEX2 gene. For information on the history of PBD complementation groups, see 214100.

Clinical Features

Shimozawa et al. (1992) studied a Japanese girl (M.M.), aged 8 months, with typical clinical findings of Zellweger syndrome as well as accumulation of very long chain fatty acids in serum, absence of liver homogenates in all 3 peroxisomal beta-oxidation enzymes, absent peroxisomes in skin fibroblasts, and, at autopsy, macrogyria and polymicrogyria in the brain, hepatosplenomegaly, and many small cysts in the renal cortices bilaterally.

Molecular Genetics

In a Japanese patient (M.M.) with Zellweger syndrome, Shimozawa et al. (1992) identified a homozygous nonsense mutation in the PEX2 gene (170993.0001). Shimozawa et al. (1993) identified this mutation in a Dutch patient with Zellweger syndrome.

In 3 patients with Zellweger syndrome, Gootjes et al. (2004) identified homozygous mutations in the PEX2 gene (170993.0001-170993.0003).