Adult Refsum disease

La maladie de Refsum fait partie du groupe des leucodystrophies et se caractérise sur le plan biochimique par une accumulation d’acide phytanique. La prévalence de la maladie est de 1 cas pour 1 000 000 ; les deux sexes sont atteints.

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 an autosomal recessive inherited disease.

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, localised in 10pter-p11.2) encoding the peroxysomal enzyme phytanoyl-CoA hydroxylase (PhyH), which alpha-oxidises phytanic acid and allows the first step of its 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.

Source: Orphanet