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Refsum disease

Orpha number ORPHA773
Synonym(s) HMSN 4
Hereditary motor and sensory neuropathy type 4
Heredopathia atactica polyneuritiformis
Phytanic acid oxidase deficiency
Prevalence 1-9 / 1 000 000
Inheritance Autosomal recessive
Age of onset Childhood
ICD-10
  • G60.1
ICD-O -
OMIM
UMLS
  • C0034960
MeSH
  • D012035
MedDRA
  • 10038275

Summary

Refsum disease, biochemically characterised by phytanic acid accumulation, belongs to the group of leucodystrophic diseases. Prevalence of the disease is of 1 case per 1 000 000 and males and females are equally affected. Initial signs usually appear around the age of 15, but they can also manifest during childhood or at the age of 30-40 years. The first symptom is hemeralopia (loss of vision in the dark), followed by episods of chronic distal motor polyneuropathy. Other associated signs include perceptive deafness, anosmia, cerebellous ataxia and sometimes, severe intellectual deficiency. Over the course of time cutaneous signs appear (ichtyosis), along with polyepiphyseal dysplasia, myocardiopathy, elevated protein in cerebrospinal fluid, and pigmentary retinitis that may result in blindness. Refsum disease is transmitted as an autosomal recessive trait. This disorder results from phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) accumulation, which leads to lesions essentially in retina, brain and peripheral nervous system. In most cases, the causative mutation is in the PHYH gene (or PAXH, localized in 10pter-p11.2) encoding the peroxysomal enzyme phytanoyl-CoA hydroxylase (PhyH), which alpha-hydroxylates phytanic acid, which is the first step in its alpha-oxidative degradation. Another mutation was recently identified in PEX7 gene, localised in 6q22-24. It codes for the peroxine 7 receptor, which allows the import of PhyH in peroxysomes. Diagnosis is brought by the biologic evidence of phytanic acid in plasma and urines. Heterozygotes can be detected. As phytanic acid comes exclusively from food (green vegetables and herbivore animals), a strict diet helps symptoms regress partly. Nevertheless, altered audition and vision as well as anosmia can persist.

Expert reviewer(s)

  • Dr Nicole BAUMANN
  • Dr J TURPIN

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Detailed information

Clinical practice guidelines
  • DE (2008)
Practical genetics
  • EN (2013,pdf)
Article for general public
  • FR (2013,pdf)
Clinical genetics review
  • EN (2010)
Disability factsheet
  • FR (2014,pdf)
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