Adult Refsum Disease (PHYH)

Adult Refsum Disease (PHYH) is a treatable peroxisomal disorder caused by phytanic-acid accumulation. Typical features include retinitis pigmentosa, anosmia, sensorineural hearing loss, peripheral neuropathy, ataxia and ichthyosis; severe biochemical decompensation can cause cardiomyopathy and life-threatening arrhythmia.
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Genetics

Autosomal recessive disease most often caused by biallelic pathogenic variants in PHYH and less commonly by PEX7 variants. The centre pipeline entry is specifically PHYH-related disease.

Molecular Mechanism

PHYH catalyzes the first step of peroxisomal alpha-oxidation of phytanic acid, which cannot undergo conventional beta-oxidation because of its 3-methyl group. Deficiency causes phytanic-acid accumulation in neural, retinal, cardiac and other lipid-rich tissues.

Therapy

Dietary restriction of phytanic acid and avoidance of fasting or rapid weight loss are effective and must begin early. Plasmapheresis or lipid apheresis is reserved for acute severe elevations, especially with arrhythmia. Established retinal and auditory damage may be irreversible.

CCP Activity

CCP is developing a PHYH-deficient model and a gene-replacement concept.

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