Refsum disease is a rare, inherited metabolic disorder impacting the body’s ability to process a specific type of fat. This condition results from a genetic inability to break down phytanic acid, a branched-chain fatty acid obtained through diet. The accumulation of this acid can lead to a range of health issues affecting multiple body systems.
Understanding Refsum Disease
Refsum disease is a peroxisomal disorder, involving a malfunction of peroxisomes, cellular organelles that break down fatty acids. This leads to phytanic acid buildup in tissues and organs. It is rare, though its true prevalence might be higher due to underdiagnosis. This accumulation gradually impairs cellular functions, particularly in the nervous system, eyes, and skin.
This disorder can appear in childhood, adolescence, or even adulthood. Its slow progression makes early diagnosis challenging. The severity and specific array of symptoms can vary significantly among affected individuals.
Causes and Mechanisms
Refsum disease is an autosomal recessive genetic disorder, meaning it requires two mutated gene copies, one from each parent. The primary gene implicated in over 90% of cases is the PHYH gene, located on chromosome 10. Mutations in the PEX7 gene account for the remaining cases.
The PHYH gene provides instructions for creating the enzyme phytanoyl-CoA hydroxylase (PhyH). This enzyme is crucial for the alpha-oxidation pathway, a peroxisomal process that breaks down phytanic acid. Mutations in PHYH reduce or eliminate this enzyme’s activity, preventing proper phytanic acid metabolism. As a result, phytanic acid accumulates in the blood and tissues, leading to cellular dysfunction and the disease’s clinical manifestations.
Recognizing the Signs
One of the earliest and most common signs is retinitis pigmentosa, an eye disorder causing night blindness and progressive peripheral vision loss, potentially leading to blindness. Loss of the sense of smell, known as anosmia, is also common.
Neurological issues are prominent, including ataxia, causing balance and coordination problems, and peripheral neuropathy, causing muscle weakness, numbness, and tingling. Some individuals may experience sensorineural hearing loss, ranging from mild to profound. Skin conditions like ichthyosis, dry, scaly skin, may also develop. Skeletal abnormalities, such as shortened bones in the fingers and toes, affect about one-third of individuals from birth. Cardiac involvement, including arrhythmias and cardiomyopathy, can also occur and pose serious risks.
Diagnosis and Management
Diagnosing Refsum disease begins with blood tests to measure phytanic acid levels, which are significantly elevated in affected individuals. Genetic testing confirms the diagnosis by identifying PHYH or PEX7 gene mutations. Other diagnostic tools, such as nerve conduction studies, ophthalmological examinations, and audiometry, help assess organ damage and guide treatment strategies.
Management primarily focuses on strictly restricting dietary intake of phytanic acid. This branched-chain fatty acid is found in foods such as ruminant meats (beef, lamb, goat), dairy products, and certain fish like cod and salmon. This diet reduces the harmful substance’s accumulation.
In severe cases or during acute crises, plasmapheresis may be used to remove excess phytanic acid from the blood for rapid reduction. While dietary modifications can significantly improve some symptoms like ichthyosis and peripheral neuropathy, certain manifestations, such as retinitis pigmentosa and hearing loss, may not fully resolve. Ongoing monitoring and symptomatic treatments are also part of comprehensive care.