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Refsum disease

Refsum disease
File:Phytanic acid.png
Classification and external resources
ICD-10 G60.1
ICD-9 356.3
OMIM 266500
DiseasesDB 11213
eMedicine derm/705
NCI Refsum disease
Patient UK Refsum disease
MeSH D012035

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]


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]


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 or remission occur. Symptoms also include ataxia, scaly skin (ichthyosis), difficulty hearing, and eye problems including cataracts and night blindness.


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.


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

External links


  1. ^ a b c Online 'Mendelian Inheritance in Man' (OMIM) 266500
  2. ^ Freedberg et al. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. p. 499. ISBN 0-07-138076-0. 
  3. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 564. ISBN 0-7216-2921-0. 
  4. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. 
  5. ^ Jayaram, H.; Downes, S. M. (March 2008). "Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report". Journal of Medical Case Reports (Free full text) 2: 80. PMC 2275283. PMID 18336720. doi:10.1186/1752-1947-2-80.  edit
  6. ^ Refsum S (1945). "Heredoataxia hemeralopica polyneuritiformis - et tidligere ikke beskrevet familiært syndrom? En foreløbig meddelelse". Nordisk Medicin (in Norwegian) 28: 2682–6. 
  7. ^ Refsum S (1946). "Heredopathia atactica polyneuritiformis. A familial syndrome not hitherto described. A contribution to the clinical study of hereditary diseases of the nervous system". Acta psych. neur. (Suppl.38): 1–303. 
  8. ^ Online 'Mendelian Inheritance in Man' (OMIM) 266510
  9. ^ National Institutes of Health. "Synonym(s): Phytanic Acid Storage Disease, Heredopathia Atactica Polyneuritiformis <Internet>". Retrieved 8 July 2007. 
  10. ^ Baldwin, R. J. et al. (2010). "The effectiveness of long-term dietary therapy in the treatment of adult Refsum disease". J Neurol Neurosurg Psychiatry 81 (9): 954–957. PMID 20547622. doi:10.1136/jnnp.2008.161059. 
  11. ^ Xu F, Ng VY, Kroetz DL, de Montellano PR (2006). "CYP4 isoform specificity in the omega-hydroxylation of phytanic acid, a potential route to elimination of the causative agent of Refsum's disease". J. Pharmacol. Exp. Ther. 318 (2): 835–9. PMID 16707724. doi:10.1124/jpet.106.104976. 
  12. ^ Verhoeven, N. M.; Wanders, R. J.; Poll-The, B. T.; Saudubray, J. M.; Jakobs, C. (1998). "The metabolism of phytanic acid and pristanic acid in man: a review". Journal of Inherited Metabolic Disease 21 (7): 697–728. PMID 9819701. doi:10.1023/A:1005476631419.  edit
  13. ^ Watkins, P. A.; Moser, A. B.; Toomer, C. B.; Steinberg, S. J.; Moser, H. W.; Karaman, M. W.; Ramaswamy, K.; Siegmund, K. D.; Lee, D. R.; Ely, J. J.; Ryder, O. A.; Hacia, J. G. (2010). "Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions". BMC Physiology 10: 19. PMC 2964658. PMID 20932325. doi:10.1186/1472-6793-10-19.  edit