Refsum disease

Refsum disease, also known as classic or adult Refsum disease, heredopathia atactica polyneuritiformis, phytanic acid oxidase deficiency and phytanic acid storage disease,^[1][2][3][4] is an autosomal recessive^[5] neurological disease that results from the over-accumulation of phytanic acid in cells and tissues. It is one of several disorders named after Norwegian neurologist Sigvald Bernhard Refsum (1907–1991).^[6][7]

Classification

Adult Refsum disease may be divided into the adult Refsum disease 1 and adult Refsum disease 2 subtypes. The former stems from mutations in the phytanoyl-CoA hydroxylase (PAHX aka PHYH) gene, while the latter stems from mutations in the peroxin 7 (PEX7) gene.^[1]

Adult Refsum disease should not be confused with infantile Refsum disease, a peroxisome biogenesis disorder resulting from deficiencies in the catabolism of very long chain fatty acids and branched chain fatty acids (such as phytanic acid) and plasmalogen biosynthesis.^[1][8]

Characteristics

Individuals with Refsum disease present with neurologic damage, cerebellar degeneration, and peripheral neuropathy. Onset is most commonly in childhood/adolescence with a progressive course, although periods of stagnation/remission occur. Symptoms also include night blindness, ataxia, scaly skin (ichthyosis), difficulty hearing, and eye problems including cataracts.

Cause

Refsum disease is a peroxisomal disorder caused by the impaired alpha-oxidation of branched chain fatty acids resulting in buildup of phytanic acid and its derivatives in the plasma and tissues. This may be due to deficiencies of phytanoyl-CoA hydroxylase or peroxin-7 activity. In general, Refsum disease is caused by PHYH mutations.

Treatment

Individuals with Refsum disease are commonly placed on a phytanic acid-restricted diet and avoid the consumption of fats from ruminant animals and certain fish.^[9][10] Recent research has shown that CYP4 isoform enzymes could help reduce the over-accumulation of phytanic acid in vivo.^[11] Plasmapheresis is another medical intervention used to treat patients.

Biological sources of phytanic acid

In ruminant animals, the gut fermentation of consumed plant materials liberates phytol, a constituent of chlorophyll, which is then converted to phytanic acid and stored in fats.^[12] Although humans cannot derive significant amounts of phytanic acid from the consumption of chlorophyll present in plant materials, it has been proposed that the great apes (bonobos, chimpanzees, gorillas, and orangutans) can derive significant amounts of phytanic acid from the hindgut fermentation of plant materials.^[13]

See also

• The Myelin Project
• List of cutaneous conditions

External links

• GeneReview/NCBI/NIH/UW entry on Refsum Disease

References