Refsum disease

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Description from OMIM

Refsum disease is an autosomal recessive inborn error of lipid metabolism classically characterized by a tetrad of clinical abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells. However, not all patients show all these features. All patients have accumulation of an unusual branched-chain fatty acid, phytanic acid, in blood and tissues. Other variable features include cardiac dysfunction, nerve deafness, ichthyosis, and multiple epiphyseal dysplasia (review by Skjeldal et al., 1987). Increased levels of phytanic acid can also be found in peroxisomal biogenesis disorders; see Zellweger syndrome (see 214100) (Skjeldal et al., 1987). Infantile Refsum disease (see PBD1B, 601539) is a distinct disorder with a different phenotype and genetic basis. A phenotype clinically indistinguishable from that of classic Refsum disease (PBD9B; 614879), but with a different biochemical profile, can be caused by mutation in the gene encoding peroxin-7 (PEX7; 601757) on chromosome 6q.



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List of symptoms



Symptom/sign Organ system Percent affected Pubmed id Added on(yyyy-mm-dd) Edit/add reference
Retinitis pigmentosa nervous 100 % 2433405 2011-10-22
Night blindness nervous 100 % 2433405 2011-10-22
Neuropathy nervous 100 % 2433405 2011-10-22
Neuropathy nervous 100 % 2433405 2011-10-22
Retinitis pigmentosa nervous 100 % 11948235 2011-10-22
Anosmia nervous 93 % 11948235 2011-10-22
Hearing loss nervous 88 % 2433405 2011-10-22
Anosmia nervous 75 % 2433405 2011-10-22
Neuropathy nervous 73 % 11948235 2011-10-22
Hearing loss nervous 67 % 11948235 2011-10-22
Cataract nervous 65 % 2433405 2011-10-22
Ataxia nervous 53 % 11948235 2011-10-22
Ichthyosis integumentary 41 % 2433405 2011-10-22
Ataxia nervous 29 % 2433405 2011-10-22
Ichthyosis integumentary 27 % 11948235 2011-10-22



List of references:


Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation.
O H Skjeldal, O Stokke, S Refsum, J Norseth, H Petit,

Phytanic acid accumulation has for more than 20 years been used as a diagnostic criterion of Refsum's disease. Recently, however, phytanic acid has also been found in peroxisomal disorders (Zellweger's syndrome, neonatal adrenoleukodystrophy, infantile Refsum's syndrome, rhizomelic chondrodysplasia punctata). The 17 patients with Refsum's disease in the present study had serum phytanic acid values differing from 73 to less than 0.5 mg/dl (normal). alpha-Oxidation of phytanic acid in skin fibroblast cultures showed a defective capacity in all, with only small differences in residual activity. Phytanic acid determinations in serum from 3 of the 7 patients with peroxisomal disorders showed slightly elevated levels in 2. The alpha-oxidation capacity in the fibroblasts was defective in all, with a residual activity similar to that of Refsum's disease. An assay of the alpha-oxidation capacity may be useful in the diagnosis of both Refsum's disease and the peroxisomal disorders. The distinction between Refsum's disease and the peroxisomal disorders can easily be done on a clinical basis.

Journal of the neurological sciences - Jan 1987



Refsum's disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation.
Anthony S Wierzbicki, Matthew D Lloyd, Christopher J Schofield, Michael D Feher, F Brian Gibberd,

Refsum's disease (hereditary motor sensory neuropathy type IV, heredopathia atactica polyneuritiformis) is an autosomal recessive disorder the clinical features of which include retinitis pigmentosa, blindness, anosmia, deafness, sensory neuropathy, ataxia and accumulation of phytanic acid in plasma- and lipid-containing tissues. The transport and biochemical pathways of phytanic acid metabolism have recently been defined with the cloning of two key enzymes, phytanoyl-CoA 2-hydroxylase (PAHX) and 2-hydroxyphytanoyl-CoA lyase, together with the confirmation of their localization in peroxisomes. PAHX, an iron(II) and 2-oxoglutarate-dependent oxygenase is located on chromosome 10p13. Mutant forms of PAHX have been shown to be responsible for some, but not all, cases of Refsum's disease. Certain cases have been shown to be atypical mild variants of rhizomelic chondrodysplasia punctata type 1a. Other atypical cases with low-plasma phytanic acid may be caused by alpha-methylacyl-CoA racemase deficiency. A sterol-carrier protein-2 (SCP-2) knockout mouse model shares a similar clinical phenotype to Refsum's disease, but no mutations in SCP-2 have been described to-date in man. This review describes the clinical, biochemical and metabolic features of Refsum's disease and shows how the biochemistry of the alpha-oxidation pathway may be linked to the regulation of metabolic pathways controlled by isoprenoid lipids, involving calcineurin or the peroxisomal proliferator activating alpha-receptor.

Journal of neurochemistry - Mar 2002