What causes Refsum disease?

Refsum disease is caused by mutations in the _PHYH_ gene, which encodes the enzyme phytanoyl-CoA hydroxylase. This enzyme is responsible for converting phytanic acid, a branched-chain fatty acid, into pristanic acid. In individuals with Refsum disease, the deficiency of phytanoyl-CoA hydroxylase results in the accumulation of phytanic acid in the body, leading to a range of symptoms and complications, including:

1. Neurological Abnormalities: Phytanic acid deposition in nerve tissues can cause a variety of neurological symptoms, including peripheral neuropathy (damage to nerves in the extremities), cerebellar ataxia (incoordination and difficulty with balance), retinitis pigmentosa (progressive degeneration of the retina leading to vision loss), and sensorineural hearing loss.

2. Skeletal Abnormalities: Refsum disease can lead to skeletal changes, such as shortening of the long bones in the limbs (micromelia) and deformities of the spine, including kyphoscoliosis (abnormal curvature of the spine).

3. Skin and Hair Changes: Individuals with Refsum disease may develop a characteristic ichthyosis (dry, scaly skin), as well as brittle hair.

4. Cardiac Abnormalities: In some cases, Refsum disease can lead to cardiomyopathy (enlarged or weakened heart muscle), arrhythmias (irregular heartbeats), and heart failure.

The severity and progression of Refsum disease can vary among affected individuals, depending on the specific genetic mutations involved. Early diagnosis and management, including dietary modifications to restrict phytanic acid intake and potentially other treatments, can help slow the progression of symptoms and improve the overall prognosis for individuals with Refsum disease.