KEGG   DISEASE: Refsum disease
Entry
H00075                      Disease                                

Name
Refsum disease;
Heredopathia atactica polyneuritiformis
Description
Refsum disease (RD) is an autosomal recessive sensory motor neuropathy charactarized by retinitis pigmentosa, peripheral neuropathy, anosmia, deafness, cerebellar ataxia and elevated protein concentrations in the cerebrospinal fluid in the absence of an increased number of cells. The age at which symptoms first present in RD can be variable although most cases present in adolescence. Because the patients are unable to metabolize phytanic acid derived from exogenous sources, highly raised plasma phytanic acid (PA) level in tissues and body fluids is the hallmark of RD. Mutant forms of phytanoyl-CoA 2-hydroxylase (PHYH) which plays a key role of phytanic acid alpha-oxidation in peroxisomes have been shown to be responsible for some, but not all, cases of Refsum's disease. Peroxisomal PHYH import occurs via PEX7 which is the peroxisomal matrix protein receptor. Though PEX7 has been identified another responsible gene, there still remain a small number of patients in whom no mutations in either of these two genes can be found.
Category
Neurodegenerative disease; Congenital disorder of metabolism; Peroxisomal disease
Brite
Human diseases [BR:br08402]
 Nervous system diseases
  Neurodegenerative diseases
   H00075  Refsum disease
 Congenital disorders of metabolism
  Peroxisomal diseases
   H00075  Refsum disease
Human diseases in ICD-11 classification [BR:br08403]
 05 Endocrine, nutritional or metabolic diseases
  Metabolic disorders
   Inborn errors of metabolism
    5C57  Peroxisomal diseases
     H00075  Refsum disease
Related
pathway
hsa04146  Peroxisome
Gene
PHYH; phytanoyl-CoA 2-hydroxylase [HSA:5264] [KO:K00477]
PEX7; peroxisomal biogenesis factor 7 [HSA:5191] [KO:K13341]
Env factor
Phytanic acid from diet
Comment
Disease class: leukodystrophy; phytanic acid storage disease
Affected region: cerebellum
Microscopic lesion: accumulation of phytanic acid
Other DBs
ICD-11: 5C57.1
ICD-10: G60.1
MeSH: D012035
OMIM: 266500
Reference
  Authors
Wierzbicki AS
  Title
Peroxisomal disorders affecting phytanic acid alpha-oxidation: a review.
  Journal
Biochem Soc Trans 35:881-6 (2007)
DOI:10.1042/BST0350881
Reference
  Authors
Wanders RJ, Komen JC
  Title
Peroxisomes, Refsum's disease and the alpha- and omega-oxidation of phytanic acid.
  Journal
Biochem Soc Trans 35:865-9 (2007)
DOI:10.1042/BST0350865
Reference
  Authors
van den Brink DM, Wanders RJ
  Title
Phytanic acid: production from phytol, its breakdown and role in human disease.
  Journal
Cell Mol Life Sci 63:1752-65 (2006)
DOI:10.1007/s00018-005-5463-y
Reference
PMID:14974078 (PEX7)
  Authors
Jansen GA, Waterham HR, Wanders RJ.
  Title
Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7).
  Journal
Hum Mutat 23:209-18 (2004)
DOI:10.1002/humu.10315
Reference
  Authors
Wierzbicki AS, Mayne PD, Lloyd MD, Burston D, Mei G, Sidey MC, Feher MD, Gibberd FB
  Title
Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease.
  Journal
J Lipid Res 44:1481-8 (2003)
DOI:10.1194/jlr.M300121-JLR200
Reference
  Authors
Wanders RJ, Jansen GA, Lloyd MD
  Title
Phytanic acid alpha-oxidation, new insights into an old problem: a review.
  Journal
Biochim Biophys Acta 1631:119-35 (2003)
DOI:10.1016/S1388-1981(03)00003-9

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