Peroxisome Biogenesis Disorder 10b

A number sign (#) is used with this entry because of evidence that peroxisome biogenesis disorder-10B (PBD10B) is caused by compound heterozygous mutation in the PEX3 gene (603164) on chromosome 6q24. One such patient has been reported.

For a discussion of genetic heterogeneity of the milder forms of PBD, see PBD1 (601539).

Clinical Features

Maxit et al. (2017) reported a 9-year-old boy with a moderately severe peroxisomal biogenesis disorder. He had neonatal jaundice that resolved spontaneously. Dysmorphic features included high forehead, posteriorly rotated and low-set ears, and inverted nipples. He had delayed psychomotor development with axial hypotonia that progressed to severe spastic paraparesis with hyperreflexia by age 4 years. He had 2 isolated seizure-like episodes that were well-controlled. Other features included nephrocalcinosis, neurogenic bladder, nystagmus, and cataracts. Laboratory studies showed mild biochemical abnormalities consistent with a peroxisomal disorder, including increased levels of very long-chain fatty acids.

Inheritance

The transmission pattern of PBD10B in the family reported by Maxit et al. (2017) was consistent with autosomal recessive inheritance.

Molecular Genetics

In a 9-year-old boy with PBD10B, Maxit et al. (2017) identified compound heterozygous mutations in the PEX3 gene (R300X, 603164.0003 and G331R, 603164.0004). Each unaffected parent was heterozygous for 1 of the mutations. Functional studies of the variants were not performed. Patient cells showed a mosaic pattern of catalase-positive particles and peroxisomal membrane structures, consistent with the milder clinical phenotype.