Refsum disease

Refsum disease is an inherited metabolic disorder in which impaired phytanic acid breakdown causes progressive retinal, neurological, and cardiac problems. The classic adult form is usually caused by biallelic variants in PHYH.

Alpha-oxidation: A fatty-acid degradation pathway that removes one carbon from the molecule’s carboxyl end. Phytanic acid requires this pathway because its beta-methyl branch blocks ordinary beta-oxidation.
Retinitis pigmentosa: A group of inherited retinal disorders that progressively damage rod and cone photoreceptors. Night blindness and narrowing visual fields often make retinal degeneration an early clue.
Plasma phytanic acid: A blood measurement of phytanic acid concentration, used to assess its accumulation in the body. Markedly elevated levels support diagnosis and can be followed during dietary treatment.
Sigvald Refsum: A Norwegian neurologist who described the disorder now known as Refsum disease. His clinical description established the disease as a distinct neurological syndrome.
Phytanoyl-CoA 2-hydroxylase: A peroxisomal enzyme that catalyzes the first step of phytanic acid alpha-oxidation. PHYH variants impair this enzyme in the most common form of the disease.
Peripheral neuropathy: Damage to nerves outside the brain and spinal cord, causing sensory or motor symptoms. Refsum disease can cause progressive weakness, numbness, and impaired coordination through peripheral nerve damage.
Dietary management of Refsum disease: A treatment approach that restricts foods rich in phytanic acid and avoids prolonged fasting. Reducing dietary phytanic acid intake can lower body stores and limit metabolic stress.
Phytanic acid: A branched-chain fatty acid found chiefly in dairy products, ruminant meat, and some fish. Identification of this accumulating molecule connected Refsum’s syndrome to a specific metabolic defect.
Peroxisome: A membrane-bound cell compartment that carries out oxidative reactions, including several steps in lipid metabolism. The blocked phytanic acid breakdown pathway operates in peroxisomes.
Anosmia: The partial or complete loss of the sense of smell. Loss of smell may precede other recognizable features of Refsum disease.

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AdrenoleukodystrophyCompared with: It is another peroxisomal metabolic disorder, but involves a different fatty acid and clinical pattern.