What is Wolfram Syndrome (DIDMOAD)?


Wolfram Syndrome also known by the acronym DIDMOAD is a genetic condition leading to juvenile diabetes in childhood, deteriorating vision due to optic atrophy and deafness. There are other associated symptoms like balance issues in the inner ear and brain, ataxic gait, bladder and bowel dysfunction, depression and anxiety issues.

The acronym DIDMOAD is taken from:

  • Diabetes insipidus (DI)
  • Diabetes mellitus (DM)
  • Optic atrophy (OA) and Deafness (D)

There is currently no cure for Wolfram syndrome and treatment is mainly supportive.

Patterns of Inheritance


Wolfram syndrome is mainly inherited in an autosomal recessive pattern where both the parents carry a mutated gene resulting in the child being affected. In some cases, autosomal dominant mutations are found. Atypical cases also include mitochondrial DNA mutations.

The genetic mutations result in mutations and loss of the wolframin protein comprising 890 amino acids. This affects pancreatic cells, neuronal and endocrine cells.

Types


The types of Wolfram syndrome are primarily distinguished by their genetic mutations:

  • Type 1 is caused by mutations in the WFS1 gene
  • Type 2 is caused by mutations in the CISD2 gene

Signs and Symptoms


The signs and symptoms of type 1 and type 2 often overlap. Type 1 (DIDMOAD) often begins with begins with diabetes insipidus (DI), childhood-onset diabetes mellitus (DM), gradual loss of vision - optic atrophy and deafness.

Type 1 and Type 2 present with the following symptoms:

  • Issues with sex hormones
  • gastrointestinal problems
  • peripheral neuropathy
  • seizures
  • psychosis and depression
  • muscle spasms
  • loss of sense of smell
  • urinary tract problems

People with Type 2 also frequently present with bleeding ulcers.

Diagnosis


The important signs and symptoms which can be picked up for easy diagnosis include:

  • Juvenile-onset diabetes (age less than 16 years)
  • Juvenile-onset optic atrophy (age less than 16 years)

It is extremely important to go in for genetic testing to confirm a diagnosis. Mutations in the gene WFS1 and CISD2 is a confirmatory test for diagnosis.

Please see list of specialized genetic testing centres

Wolfram syndrome
Genetic testing is available to detect genetic mutations of Wolfram syndrome
Image Source: Pixabay

Treatment and Management


Currently, no permanent cure is available for Wolfram syndrome. Treatment is mainly supportive and depends on the signs and symptoms in each person. Almost all children and adults diagnosed with diabetes will have to be on lifelong insulin therapy. Those who suffer from hearing loss may benefit with hearing aids or cochlear transplants.

Other symptoms like bladder dysfunction, gastrointestinal issues, sleep disturbances and depression should be managed with medications.

Wolfram syndrome should be managed by a multidisciplinary medical team.

Look up our list of patient organizations in India for help and support

Prenatal Testing and Wolfram Syndrome


If there is a known case of Wolfram syndrome in the family, it is absolutely essential for closest female relatives like siblings, uncles, aunts and cousins to test for carrier status.

If a woman with a carrier status is pregnant, prenatal test is essential to determine if the fetus has the disease mutation.

Look up our list of clinical geneticists and testing centres in India for help and support

Mail us on namitha@strandlf.org if you require any further information or want to contribute a resource for this page

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