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Refsum Disease

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Synonyms of Refsum Disease

Disorder Subdivisions

General Discussion

Refsum disease is one of a family of genetic disorders known as the leukodystrophies in which, as a consequence of the disruption of lipid metabolism, the myelin sheath that insulates and protects the nerves of the brain fails to grow. It is inherited as an autosomal recessive trait. It is characterized by progressive loss of vision (retinitis pigmentosa); degenerative nerve disease (peripheral neuropathy); failure of muscle coordination (ataxia); and dry, rough, scaly skin (ichthyosis).

The disorder is caused by the accumulation of a particular fatty acid (phytanic acid) in blood plasma and tissues. This occurs because of a malfunction of the gene that makes the enzyme that breaks down (metabolizes) this acid. The essential enzyme is absent.

Treatment with a diet low in foods that contain phytanic acid can be beneficial. Our bodies cannot make phytanic acid. Instead, it is introduced to the body in certain foods, including dairy products, beef, lamb and some seafood.


Symptoms of Refsum disease may include vision impairment, degenerative nerve disease, failure of muscle coordination, and bone and skin changes. Symptoms may include night blindness, loss of peripheral vision, and numbness and weakness associated with failure of muscle coordination.

Affected individuals may experience an unusual burning or prickling sensation (paresthesia) of arms and legs. Neurological symptoms include unsteady walking with frequent falls (ataxia), and peripheral neuropathy (characterized by sensory, motor, and reflex changes). Skin changes may include dryness, itchiness, and scaliness.

An infantile form of Refsum disease exists that usually becomes apparent during the first year of life. In addition to early onset, it is characterized by developmental delay, vision and hearing impairment, enlargement of the liver and defective metabolism of bile acid.


Refsum disease is inherited as a recessive trait. The genes responsible for the failure in the metabolism of phytanic acid have been traced to the short arm of chromosome 10 (10pter-p11.2) and the long arm of chromosome 6 (6q22-q24).

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 6q22" refers to band 22 on the long arm of chromosome 6. The notation "10pter" refers to the end or terminus of the short arm of chromosome 10. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

The age of onset of Refsum disease varies greatly. It may occur at any time from early childhood until around 50 years of age, but in most symptoms will have appeared by age 20. Males and females are affected in equal numbers.

Related Disorders

There are many disorders caused by abnormal lipid metabolism. Acanthocytosis, also known as Lipoprotein Deficiency, is inherited as a recessive trait, and tends to occur more than once in families where it is found. This rare disorder usually begins in the first year of life and is marked by malnutrition, growth retardation, abdominal distention, and progressive neurological dysfunction. Curvature of the spine, muscle coordination impairment (ataxia), and eye problems including pigmentary retinal degeneration beginning at about ten years of age may also be symptomatic of Acanthocytosis.

Gaucher's Disease is an inherited disease of lipid metabolism caused by the failure to produce the enzyme glucocerebrosidase. It is the most common of the fourteen known lipid storage disorders which includes Tay-Sachs Disease, Fabry's Disease, and Niemann-Pick Disease. There are three types of Gaucher's Disease - Type I, II, and III. All three are characterized by the presence of Gaucher (lipid-laden) cells in the bone marrow and other organs such as the spleen and liver.

Tay-Sachs Disease is an infantile form of Ceroid-Lipofuscinosis. Tay-Sachs is a genetic disorder that causes the progressive destruction of the central nervous system. It is generally found among children of Eastern European Jewish heritage and becomes clinically apparent at about six months of age.

Niemann-Pick Disease is a rare, familial disorder of lipid metabolism characterized by the accumulation of sphingomyelin and cholesterol in the reticuloendothelial cells. There are at least five different forms of this type of lipidosis.

(For more information on these disorders, choose "Gaucher," "Tay-Sach," "Fabry", "Niemann" and "Acanthocytosis" as your search terms in the Rare Disease Database.)

Standard Therapies

The presence of phytanic acid in blood or urine samples is diagnostic.

Treatment of Refsum disease involves following a strict diet low in phytanic acid (found in dairy products, beef, lamb and some seafoods) and high in calories. The removal and reinfusion of blood plasma (plasmapheresis) may also be required. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

High doses of vitamin A are thought by some researchers to retard the rate of degradation of eyesight in retinitis pigmentosa associated with classical (adult-onset) Refsum disease.

Refsum Disease Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:


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Report last updated: 2008/02/21 00:00:00 GMT+0