Refsum disease is a rare, autosomal recessive, lipid metabolism disorder caused by a deficiency of phytanoyl-CoA hydroxylase, leading to the accumulation of phytanic acid in plasma and tissues. Most cases are due to mutations in the PHYH or PEX7 gene. Prevalence is estimated to be 1 in 1 000 000, with cases primarily reported in individuals of Scandinavian, northern French, British, and Irish descent. Symptoms usually begin in late childhood or adolescence (although late-onset forms have been described in patients in their 50s), and progression is usually indolent, although acute and subacute cases have also been described. Hallmark clinical findings include retinitis pigmentosa, polyneuropathy with symmetrical distal-gradient weakness, cerebellar ataxia, and elevated cerebrospinal fluid (CSF) protein levels. Other neurological features include anosmia and hearing loss. Cardiac manifestations include arrhythmias and cardiomyopathy, and skeletal abnormalities, such as shortened metacarpals and/or metatarsals and epiphyseal dysplasia, occur. Dermatologically, scaling and ichthyosis may be seen on the trunk and extremities. In most cases, the ichthyosis resembles ichthyosis vulgaris, but in more severe cases, it may resemble lamellar ichthyosis. There is also prominence of palmoplantar markings.

Shortened metacarpals and/or metatarsals, if present, are apparent at birth. In early childhood, night blindness due to retinitis pigmentosa develops, often progressing to severe visual impairment over time. Onset of scaling occurs in adolescence. As the disease progresses into later stages, neurological symptoms such as peripheral neuropathy, ataxia, and hearing loss gradually emerge.