Peroxisome Biogenesis Disorder 3B (Infantile Refsum Disease)

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

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).

Treatment
Treatment Options: 

No effective treatment is known.

References
Article Title: 

References

Matsui S, Funahashi M, Honda A, Shimozawa N. Newly identified milder phenotype of peroxisome biogenesis disorder caused by mutated PEX3 gene. Brain Dev. 2012 Dec 13.  [Epub ahead of print].

PubMedID: 23245813

Waterham HR, Ebberink MS. Genetics and molecular basis of human peroxisome biogenesis disorders. Biochim Biophys Acta. 2012 Sep;1822(9):1430-41.

PubMedID: 22871920

Goez H, Meiron D, Horowitz J, Schutgens RH, Wanders RJ, Berant M, Mandel H. Infantile Refsum disease: neonatal cholestatic jaundice presentation of a peroxisomal disorder. J Pediatr Gastroenterol Nutr. 1995 Jan;20(1):98-101.

PubMedID: 7533834

Wanders RJ, Saelman D, Heymans HS, Schutgens RB, Westerveld A, Poll-Th?(c) BT, Saudubray JM, Van den Bosch H, Strijland A, Schram AW, et al. Genetic relation between the Zellweger syndrome, infantile Refsum's disease, and rhizomelic chondrodysplasia punctata. N Engl J Med. 1986 Mar 20;314(12):787-8.

PubMedID: 2419755