What is Refsum disease?

Quick Answer
Refsum disease is a severe, progressive inherited disorder that results in symptoms such as pain, difficulty walking, heart failure, skin issues, and/or loss of the ability to smell, see, and hear. The features of the disease are caused by the harmful buildup of fatty substances in the body and brain.
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Risk Factors

Refsum disease is a genetic condition caused by the inheritance of the same nonworking gene from both parents. Most cases of Refsum disease have been reported in the United Kingdom and Norway. The incidence of the condition is very low. In the United Kingdom, the disease is found in approximately 1 in 1,000,000 individuals. This condition is not caused by infections and cannot be transmitted by an affected individual.

Etiology and Genetics

Refsum disease is caused by the buildup of a substance called phytanic acid in the cells of the body. This abnormal buildup is caused by either the lack of an enzyme called phytanoyl-CoA hydroxylase or a decreased quantity of a critical cell part called the peroxisome-targeting signal type 2 receptor. When the enzyme or the receptor is missing, the accumulation of the phytanic acid in the cells, tissues, and body fluids results in the inability of the brain and body to work correctly.

Refsum disease is an autosomal recessive genetic condition, which manifests when a child receives two copies of a nonworking gene. Individuals with only one copy of the nonworking gene are known as carriers and have no problems related to the condition. There are two known genes that can cause Refsum disease: PHYH, which is located at 10p13 and is responsible for more than 90 percent of cases, and PEX7, which is located at 6q23.3 and is responsible for the rest.


The symptoms of Refsum disease involve progressive deterioration of motor and neurocognitive function, including loss of smell, loss of physical milestones, a type of early-onset blindness called retinitis pigmentosa, nerve disorders (neuropathy), pain, deafness, stumbling gait, enlarged heart, heart arrhythmia, and cardiac failure. However, the severity and time of onset of these symptoms vary significantly from person to person. It is rare to see all of the symptoms of Refsum disease in one individual.

The onset of Refsum disease can occur from seven months of age to mid-adulthood. The most common time of onset is late childhood. Symptoms often start with loss of the sense of smell (anosmia) and progressive loss of vision caused by retinal degeneration (retinitis pigmentosa). Over the next ten to fifteen years, as the disease progresses, affected individuals will often develop difficulty walking (ataxia); skin issues (ichthyosis); weakness, pain, and numbness from nerve malfunction (peripheral neuropathy); and possibly shortened finger or toe bones. Death most often occurs as a result of cardiac failure.

Screening and Diagnosis

Genetic screening for Refsum disease is not part of routine testing in the prenatal or newborn periods of life. Diagnosis is most often made on the basis of disease signs and symptoms such as anosmia, ataxia, and retinitis pigmentosa. Biochemical testing is available to confirm the diagnosis through a combination of elevated phytanic acid and related chemicals or low or missing amounts of phytanoyl-CoA hydroxylase. However, molecular genetic testing for nonworking PHYH and PEX7 genes is the most definitive test available.

Treatment and Therapy

There is no known cure for Refsum disease. Chronic treatment of the condition relies on a special diet that removes phytanic acid intake, avoidance of sudden weight loss, and careful monitoring for cardiac arrhythmias and other heart abnormalities by a cardiologist. Other symptoms would be treated individually, such as by using hydrating creams for skin issues. When a fast decrease in symptom-causing phytanic acid levels is required, a treatment called plasmapheresis is sometimes used to quickly reduce the amount of phytanic acid in the blood. Use of ibuprofen must be avoided in individuals affected by Refsum disease, as it may interfere with the breakdown of phytanic acid.

A few approaches for treating the underlying lack of enzyme that causes Refsum disease, such as enzyme replacement therapy, are under investigation, but these are not yet approved by the Food and Drug Administration (FDA) for use in affected individuals.

Prevention and Outcomes

Carrier testing is available for individuals who are interested in learning if they carry a nonworking PHYH or PEX7 gene. Genetic counseling is available for parents who have an affected child or are concerned about being a carrier for a nonworking PHYH or PEX7 gene. As the severity and symptoms of Refsum disease vary from individual to individual, life expectancy depends on the ability to follow the special low-phytanic-acid diet as well as the speed of progression of the disease.


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