OMIM ID:
Peroxisome Biogenesis Disorder 3B (Infantile Refsum Disease)
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This peroxisomal disorder presents in the first year of life with both systemic and ocular features. Night blindness is the major ocular feature and at least some have optic atrophy similar to the adult form. Nystagmus may be present. Reduction or absence of rod responses on ERG can be used in young children to document the retinopathy. Blindness and deafness commonly occur in childhood.
Systemic Features
This disorder is classified as a peroxisomal biogenesis disorder (PBD) associated with the breakdown of phytanic acid. Ataxia and features of motor neuron disease are evident early. Hepatomegaly and jaundice may also be an early diagnostic feature as bile acid metabolism is defective. Infant hypotonia is often seen. Nonspecific facial dysmorphism has been reported as a feature. The teeth are abnormally large and often have yellowish discoloration. Postural unsteadiness is evident when patients begin walking. Diagnosis can be suspected from elevated serum phytanic and pipecolic acid (in 20% of patients) or by demonstration of decreased phytanic acid oxidation in cultured fibroblasts. Other biochemical abnormalities such as hypocholesterolemia and elevated very long chain fatty acids and trihydroxycholestanoic acid are usually present. Anosmia and mental retardation are nearly universal features. Early mortality in infancy or childhood is common although some survive into the 2nd and 3rd decades.
Genetics
Inheritance
This is an autosomal recessive peroxisomal biogenesis disorder (PBD) resulting from mutations in a number of PEX genes (PEX1, PEX2, PEX3, PEX12, PEX26). It shares many features with other PBDs including those formerly called Zellweger syndrome (214100), rhizomelic chondrodysplasia punctata (215100), and neonatal adrenoleukodystrophy (601539).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.