Adult Refsum disease

Adult Refsum disease (ARD), also known as classic Refsum disease, heredopathia atactica polyneuritiformis, or phytanic acid storage disease, is a rare inherited disorder of lipid metabolism caused by the accumulation of phytanic acid in blood and tissues. The condition results from a deficiency of the peroxisomal enzyme phytanoyl-CoA hydroxylase (encoded by the PHYH gene) or, less commonly, defects in the PEX7 gene, which is required for importing the enzyme into peroxisomes. Phytanic acid, a branched-chain fatty acid derived exclusively from dietary sources (dairy products, ruminant fats, and certain fish), cannot be properly broken down and accumulates in multiple organ systems. The disease primarily affects the nervous system, eyes, skin, heart, and bones. Cardinal clinical features include retinitis pigmentosa (causing progressive night blindness and visual field constriction), peripheral polyneuropathy (with distal weakness, sensory loss, and absent deep tendon reflexes), cerebellar ataxia, and elevated cerebrospinal fluid protein without increased cell count (albuminocytologic dissociation). Additional features may include ichthyosis (dry, scaly skin), anosmia (loss of smell), sensorineural hearing loss, cardiac arrhythmias and cardiomyopathy, and skeletal abnormalities such as shortened metacarpals or metatarsals. Symptoms typically begin in late childhood or early adulthood, though onset is variable. The cornerstone of treatment is strict lifelong dietary restriction of phytanic acid, which involves limiting intake of dairy fats, ruminant meat fat, and certain fish. When adhered to consistently, dietary management can lower plasma phytanic acid levels, stabilize or improve neurological symptoms, and prevent disease progression. Plasmapheresis or lipid apheresis may be used in acute situations or when phytanic acid levels are dangerously elevated, to rapidly reduce circulating phytanic acid. Rapid weight loss and fasting should be avoided, as mobilization of fat stores can release stored phytanic acid and precipitate acute neurological or cardiac crises. With early diagnosis and consistent dietary management, prognosis can be significantly improved, though existing damage to the retina and nerves may be irreversible.

Common questions about Adult Refsum disease