H number H00075
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; Inherited metabolic disease; Peroxisomal disease
Pathway hsa04146
Gene PHYH; phytanoyl-CoA 2-hydroxylase [HSA:5264] [KO:K00477]
PEX7; peroxisomal biogenesis factor 7 [HSA:5191] [KO:K13341]
Carcinogen -
Env factor Phytanic acid from diet
Pathogen -
Marker Phytanic acid [CPD:C01607]
Drug -
Comment Disease class: leukodystrophy; phytanic acid storage disease
Affected region: cerebellum
Microscopic lesion: accumulation of phytanic acid
Reference PMID: 17956237
Wierzbicki AS
Peroxisomal disorders affecting phytanic acid alpha-oxidation: a review.
Biochem Soc Trans 35:881-6 (2007)

PMID: 17956234
Wanders RJ, Komen JC
Peroxisomes, Refsum's disease and the alpha- and omega-oxidation of phytanic acid.
Biochem Soc Trans 35:865-9 (2007)

PMID: 16799769
van den Brink DM, Wanders RJ
Phytanic acid: production from phytol, its breakdown and role in human disease.
Cell Mol Life Sci 63:1752-65 (2006)

PMID: 14974078 (PEX7)
Jansen GA, Waterham HR, Wanders RJ.
Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7).
Hum Mutat 23:209-18 (2004)

PMID: 12700346
Wierzbicki AS, Mayne PD, Lloyd MD, Burston D, Mei G, Sidey MC, Feher MD, Gibberd FB
Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease.
J Lipid Res 44:1481-8 (2003)

PMID: 12633678
Wanders RJ, Jansen GA, Lloyd MD
Phytanic acid alpha-oxidation, new insights into an old problem: a review.
Biochim Biophys Acta 1631:119-35 (2003)