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

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.

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.

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.

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.