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Wolfram syndrome


Other Names for this Disease

  • Diabetes insipidus and mellitus with optic atrophy and deafness
  • DIDMOAD
  • DIDMOAD syndrome
  • WFS
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Overview

What is Wolfram syndrome?

What are the signs and symptoms of Wolfram syndrome?

What causes Wolfram syndrome?

Is Wolfram syndrome inherited?

Is genetic testing available for Wolfram syndrome?

How is Wolfram syndrome diagnosed?

How might Wolfram syndrome be treated?

What is the long-term outlook for people with Wolfram syndrome?

What is Wolfram syndrome?

Wolfram syndrome, which is also known by the acronym DIDMOAD, is an inherited condition characterized by diabetes insipidus (DI), childhood-onset diabetes mellitus (DM), a gradual loss of vision caused by optic atrophy (OA), and deafness (D).[1] There are two types of Wolfram syndrome (type 1 and type 2) which are primarily differentiated by their genetic cause. Type 1 is caused by changes (mutations) in the WFS1 gene, while type 2 is caused by mutations in the CISD2 gene. Both forms are inherited in an autosomal recessive manner.[2][3] Treatment is symptomatic and supportive.[2]
Last updated: 12/8/2014

What are the signs and symptoms of Wolfram syndrome?

There are two types of Wolfram syndrome (type 1 and type 2) which have many overlapping features. Wolfram syndrome type 1, which is also known by the acronym DIDMOAD, is characterized by diabetes insipidus (DI), childhood-onset diabetes mellitus (DM), gradual loss of vision due to optic atrophy (OA), and deafness (D).[1] About 65% of affected people will develop all four of these symptoms, while others will only have some of the associated health problems.[4]

Other signs and symptoms of Wolfram syndrome type 1 may include:[4][1][5]

In addition to the signs and symptoms found in Wolfram syndrome type 1, people with Wolfram syndrome type 2 may also have stomach and/or intestinal ulcers; and a tendancy to bleed excessivly after injuries.[1]  

Last updated: 12/8/2014

What causes Wolfram syndrome?

There are two types of Wolfram syndrome (type 1 and type 2) which are primarily differentiated by their genetic cause. Changes (mutations) in the WFS1 gene are responsible for approximately 90% of Wolfram syndrome type 1 cases. This gene encodes wolframin, a protein that is important for the proper functioning of the endoplasmic reticulum (the part of a cell that is involved in protein production, processing, and transport). Wolframin helps regulate the amount of calcium in cells, which is important for many different cellular functions. Mutations in WFS1 result in a defective form of wolframin that is unable to perform its normal role. This causes cells to trigger their own death (apoptosis). The death of cells in various organs and other parts of the body results in the signs and symptoms of Wolfram syndrome type 1.[1]

A specific mutation in the CISD2 gene causes Wolfram syndrome type 2. Although the exact function of this gene is not known, scientists suspect that it plays an important role in the mitochondria (the part of the cell where energy is produced). Mutations in CISD2 lead to the loss of mitochondria which decreases the amount of energy available to cells. Cells that do not have enough energy die. As in Wolfram syndrome type 1, the death of cells in different parts of the body results in the many health problems associated with Wolfram syndrome type 2.[1]

Mutations in mitochondrial DNA may also be a rare cause of Wolfram syndrome in some families.[6]
Last updated: 12/8/2014

Is Wolfram syndrome inherited?

Wolfram syndrome is inherited in an autosomal recessive manner.[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.
Last updated: 12/8/2014

Is genetic testing available for Wolfram syndrome?

Yes. Clinical genetic testing is available for changes (mutations) in WFS1 and CISD2, the two genes known to cause Wolfram syndrome type 1 and Wolfram syndrome type 2, respectively.[1][3] Carrier testing for at-risk relatives and prenatal testing are possible if the two disease-causing mutations in the family are known.

The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. It offers information on genetic testing for Wolfram syndrome type 1 and Wolfram syndrome type 2. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Last updated: 12/8/2014

How is Wolfram syndrome diagnosed?

A diagnosis of Wolfram syndrome is based on the presence of characteristic signs and symptoms. The identification of a change (mutation) in the WFS1 gene or CISD2 gene confirms the diagnosis.[2][5]
Last updated: 12/8/2014

How might Wolfram syndrome be treated?

Treatment of Wolfram syndrome is supportive and based on the signs and symptoms present in each person. For example, almost all affected people require insulin to treat diabetes mellitus. People with hearing loss may benefit from hearing aids or cochlear implantation.[2][4][5]

For more detailed information regarding the treatment and management of Wolfram syndrome, click here.
Last updated: 12/8/2014

What is the long-term outlook for people with Wolfram syndrome?

The long-term outlook (prognosis) for people with Wolfram syndrome varies depending on the signs and symptoms present in each person. All the features that give Wolfram syndrome the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) are observed in 65% of people, while others only have some of the associated health problems. Most affected people develop diabetes mellitus and optic atrophy before age 15 years. Hearing loss is present in 64% of affected people by age 20 years and up to 72% will eventually develop diabetes insipidus. Wolfram syndrome may also be associated with a variety of other symptoms that can affect almost every part of the body.[4][2]

Wolfram syndrome is often fatal by mid-adulthood (average lifespan 30 to 40 years) due to complications from the various health problems associated with the condition.[7]
Last updated: 12/8/2014

References
  1. Wolfram syndrome. Genetics Home Reference. 2012; http://ghr.nlm.nih.gov/condition/wolfram-syndrome. Accessed 1/21/2014.
  2. Tranebjærg L, Barrett T & Rendtorff ND. WFS1-Related Disorders. Gene Reviews. 2013; http://www.ncbi.nlm.nih.gov/books/NBK4144/. Accessed 1/21/2014.
  3. Wolfram Syndrome 2. OMIM. September 2014; http://omim.org/entry/604928.
  4. Wolfram syndrome. Orphanet. September 2014; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3463.
  5. Wolfram Syndrome. NORD. May 2008; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/850/viewFullReport.
  6. Wolfram Syndrome, Mitochondrial Form. OMIM. September 2013; http://www.omim.org/entry/598500?search=wolfram%20syndrome&;highlight=syndromic%20syndrome%20wolfram.
  7. de Heredia ML, Clèries R, Nunes V. Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype. Genet Med. 2013 Jul;15(7):497-506. July 2013; 15(7):497-506.


Other Names for this Disease
  • Diabetes insipidus and mellitus with optic atrophy and deafness
  • DIDMOAD
  • DIDMOAD syndrome
  • WFS
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.