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Genetics Home Reference: your guide to understanding genetic conditions
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Refsum disease

Reviewed January 2010

What is Refsum disease?

Refsum disease is an inherited condition that causes vision loss, absence of the sense of smell (anosmia), and a variety of other signs and symptoms.

The vision loss associated with Refsum disease is caused by an eye disorder called retinitis pigmentosa. This disorder affects the retina, the light-sensitive layer at the back of the eye. Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. The first sign of retinitis pigmentosa is usually a loss of night vision, which often becomes apparent in childhood. Over a period of years, the disease disrupts side (peripheral) vision and may eventually lead to blindness.

Vision loss and anosmia are seen in almost everyone with Refsum disease, but other signs and symptoms vary. About one-third of affected individuals are born with bone abnormalities of the hands and feet. Features that appear later in life can include progressive muscle weakness and wasting; poor balance and coordination (ataxia); hearing loss; and dry, scaly skin (ichthyosis). Additionally, some people with Refsum disease develop an abnormal heart rhythm (arrhythmia) and related heart problems that can be life-threatening.

How common is Refsum disease?

The prevalence of Refsum disease is unknown, although the condition is thought to be uncommon.

What genes are related to Refsum disease?

More than 90 percent of all cases of Refsum disease result from mutations in the PHYH gene. The remaining cases are caused by mutations in a gene called PEX7.

The signs and symptoms of Refsum disease result from the abnormal buildup of a type of fatty acid called phytanic acid. This substance is obtained from the diet, particularly from beef and dairy products. It is normally broken down through a process called alpha-oxidation, which occurs in cell structures called peroxisomes. These sac-like compartments contain enzymes that process many different substances, such as fatty acids and certain toxic compounds.

Mutations in either the PHYH or PEX7 gene disrupt the usual functions of peroxisomes, including the breakdown of phytanic acid. As a result, this substance builds up in the body's tissues. The accumulation of phytanic acid is toxic to cells, although it is unclear how an excess of this substance affects vision and smell and causes the other specific features of Refsum disease.

Related Gene(s)

Changes in these genes are associated with Refsum disease.

  • PEX7
  • PHYH

How do people inherit Refsum disease?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Refsum disease?

These resources address the diagnosis or management of Refsum disease and may include treatment providers.

  • Gene Review: Refsum Disease (http://www.ncbi.nlm.nih.gov/books/NBK1353)
  • Gene Review: Retinitis Pigmentosa Overview (http://www.ncbi.nlm.nih.gov/books/NBK1417)
  • Genetic Testing Registry: Phytanic acid storage disease (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0034960)
  • MedlinePlus Encyclopedia: Retinitis Pigmentosa (http://www.nlm.nih.gov/medlineplus/ency/article/001029.htm)

You might also find information on the diagnosis or management of Refsum disease in Educational resources (http://www.ghr.nlm.nih.gov/condition/refsum-disease/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/refsum-disease/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Refsum disease?

You may find the following resources about Refsum disease helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Refsum disease?

  • adult Refsum disease
  • ARD
  • classic Refsum disease
  • CRD
  • hereditary motor and sensory neuropathy Type IV
  • heredopathia atactica polyneuritiformis
  • HMSN IV
  • HMSN type IV
  • phytanic acid storage disease
  • Refsum's disease
  • Refsum syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Refsum disease?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Refsum disease?

acids ; anosmia ; arrhythmia ; ataxia ; autosomal ; autosomal recessive ; breakdown ; cell ; dysplasia ; fatty acids ; gene ; hereditary ; ichthyosis ; inherited ; leukodystrophy ; motor ; neuropathy ; oxidation ; peripheral ; peroxisomes ; prevalence ; recessive ; retina ; sensory neuropathy ; sign ; syndrome ; toxic ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Gene Review: Refsum Disease (http://www.ncbi.nlm.nih.gov/books/NBK1353)
  • Jansen GA, Waterham HR, Wanders RJ. Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). Hum Mutat. 2004 Mar;23(3):209-18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14974078?dopt=Abstract)
  • Van den Brink DM, Brites P, Haasjes J, Wierzbicki AS, Mitchell J, Lambert-Hamill M, de Belleroche J, Jansen GA, Waterham HR, Wanders RJ. Identification of PEX7 as the second gene involved in Refsum disease. Adv Exp Med Biol. 2003;544:69-70. (http://www.ncbi.nlm.nih.gov/pubmed/14713215?dopt=Abstract)
  • van den Brink DM, Wanders RJ. Phytanic acid: production from phytol, its breakdown and role in human disease. Cell Mol Life Sci. 2006 Aug;63(15):1752-65. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16799769?dopt=Abstract)
  • Wanders RJ, Jansen GA, Skjeldal OH. Refsum disease, peroxisomes and phytanic acid oxidation: a review. J Neuropathol Exp Neurol. 2001 Nov;60(11):1021-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11706932?dopt=Abstract)
  • Wanders RJ, Komen JC. Peroxisomes, Refsum's disease and the alpha- and omega-oxidation of phytanic acid. Biochem Soc Trans. 2007 Nov;35(Pt 5):865-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17956234?dopt=Abstract)
  • Wierzbicki AS, Lloyd MD, Schofield CJ, Feher MD, Gibberd FB. Refsum's disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation. J Neurochem. 2002 Mar;80(5):727-35. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11948235?dopt=Abstract)
  • Wierzbicki AS. Peroxisomal disorders affecting phytanic acid alpha-oxidation: a review. Biochem Soc Trans. 2007 Nov;35(Pt 5):881-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17956237?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2010
Published: November 24, 2014