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 ... 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 PEX2 gene have cells of complementation group 5 (CG5, equivalent to CG10 and CGF). For information on the history of PBD complementation groups, see 214100.
Shimozawa et al. (1999) investigated a patient with IRD, a Welsh female who presented at the age of 1 year with delayed milestones and joint laxity. Later, retinitis pigmentosa manifested and biochemical investigation showed accumulation of very long ... Shimozawa et al. (1999) investigated a patient with IRD, a Welsh female who presented at the age of 1 year with delayed milestones and joint laxity. Later, retinitis pigmentosa manifested and biochemical investigation showed accumulation of very long chain fatty acids (VLCFAs) and phytanic acid and an abnormal bile acid profile. The activities of dihydroxyacetone phosphate acyltransferase (DHAP-AT) were reduced in platelets and fibroblasts. The patient died at 3 years of age following an episode of bronchiolitis.
In a Welsh patient with IRD, Shimozawa et al. (1999) detected compound heterozygosity for a missense mutation (170993.0002) and a nonsense mutation (170993.0001) in the PEX2 gene.