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Wolfram syndrome

Also known as: DIDMOAD, Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, Deafness

Background

Wolfram syndrome is a rare and complex genetic condition, which is sometimes referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy (see entry vision disorders in childhood) and deafness). It is classified as a progressive neurodegenerative disease (a disorder that primarily affects the body's nervous system causing its ability to work correctly to gradually decline). By definition, all people with Classical Wolfram syndrome have both optic atrophy (blindness) and childhood-onset diabetes mellitus (onset under 16 years of age). A significant number also develop diabetes insipidus, and roughly two-thirds develop some degree of deafness, which is usually not severe. Individuals with Wolfram syndrome may also experience problems with the urinary tract, neurological symptoms and psychiatric illness (see entry Mental Health). There are also an increasing number of people affected by Wolfram-related disorders, in which one or more of the clinical complications are present with at least one mutation in the Wolfram gene. These people have a widely variable disease and variable rate of progression.

Credits

Last updated July 2015 by Dr Timothy G Barrett, Consultant Paediatric Endocrinologist, Birmingham Children's Hospital, Birmingham, UK.

What are the symptoms?

Wolfram syndrome is characterised by:

  • diabetes insipidus - an inability to concentrate urine because of insufficient production of vasopressin (an antidiuretic hormone)
  • diabetes mellitus - an inability to convert glucose into energy the body can use. Affected people can feel thirsty and pass lots of urine. Insulin injections are essential to treat this form of diabetes
  • optic atrophy - nerve damage to the eye
  • loss of hearing with a weakening of sound frequency, intensity, tone and pitch. This may be caused by damage to the optic nerve connecting each ear to the brain.

Other symptoms that are sometimes present in Wolfram syndrome include:

  • chronic fatigue, persistent low levels of energy and a need for increased amounts of sleep
  • a form of epilepsy characterised by sudden muscle jerks without loss of consciousness (myoclonus)
  • urinary tract disorders, such as frequent urination, incontinence and bed wetting
  • colour blindness (the inability to detect and identify colours accurately). This can occur early on and may be the first sign that there is a problem with the eyes
  • emotional, behavioural and sometimes psychiatric disorders
  • delayed sexual development, more common in boys
  • digestive disorders, such as constipation or diarrhoea. Occasionally this can be severe swallowing problems. Dysfunctions in the autonomic nerves that control digestive functions may cause these symptoms
  • neurological problems owing to damage to the nervous system causing a variety of malfunctions and disorders such as ataxia (tendency to lose balance), sudden muscle jerks, abnormal eye movements, breathing problems and dizziness.

This is a list of conditions that have been reported in patients with Wolfram syndrome; most patients do not get all of these conditions, and some patients experience very few of these.

What are the causes?

Wolfram syndrome is usually caused by a mutation or defect in the WFS1 gene. This defect affects the production and function of Wolframin, a protein found all over the body and used in almost all cells.

How is it diagnosed?

If insulin-dependent diabetes mellitus and optical atrophy symptoms are present by fifteen years of age, Wolfram syndrome is presumed to exist. Genetic testing can confirm the presence of Wolfram syndrome in about 90% of patients with these features.

How is it treated?

The condition is managed by treating the symptoms as they appear. Management of diabetes mellitus can be achieved by insulin prescription, glucose monitoring and changes to diet and exercise. There is no known treatment for optic atrophy. A hearing aid may be used to alleviate hearing loss. Anticonvulsant medication is administered to avoid seizures. A tube or catheter (device used to pass urine from the bladder) may be used several times a day to eliminate urine from the bladder to prevent urine backup and incontinence (loss of bladder control). Antidepressants and psychotherapy may be used to treat depression.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Wolfram syndrome is an autosomal recessive disorder caused by a defect in the WSF1 gene.

Prenatal diagnosis
Prenatal diagnosis for Wolfram syndrome can be conducted and involves molecular analysis of the WFS1 gene. Genetic testing is available on the NHS; the central laboratory providing this is The Regional Genetics Laboratory, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TT.

References

Barrett TG, Bundey SE. Wolfram (DIDMOAD) syndrome. J Med Genet. 1997;34:838-41.

Khanim F, Kirk J, Latif F, et al. WFS1/wolfram in mutations, Wolfram syndrome, and associated diseases. Hum Mutat. 2001;17:357-67.

Kredit M. Diabetes insipidus. CME. 2004;22:410-411.

Megighian D, Savastano M. Wolfram syndrome. Int J Pediatr Otorhinolaryngol. 2004;68:243-7.

Pilz D, Quarrell OW, Jones EW. Mitochondrial mutation commonly associated with Leber's hereditary optic neuropathy observed in a patient with Wolfram syndrome (DIDMOAD). J Med Genet. 1994;31:328-30.

Ryan EA. Treating Diabetes Mellitus. The Canadian Journal of CME. 2004:Sept;103-108.

Is there support?

WellChild Wolfram Syndrome Family Coordinator

Tel: 01242 548 762
Email: rachelbates@wellchild.org.uk
www.wellchild.org.uk/what-we-do/supporting-wolfram-families/

Established in 2012, the WellChild Wolfram Syndrome Family Coordinator provides a listening ear, gives advice and information, and links families to each other and local services. The service is available to families with children under 18 with the syndrome. The Family Coordinator is able to refer children to specialist clinics at Birmingham Children's Hospital and can act as an advocate for families' needs.

Group details last updated July 2015.

Wolfram Syndrome UK Support Group

Tel: 01903 211 358
Email: families@wolframsyndrome.co.uk
www.wolframsyndrome.co.uk

The Group is a Registered Charity in England and Wales No. 1152445. It provides information and support to families affected by Wolfram Syndrome in the UK. The Group offers an online forum and holds an annual meeting for families and medical professionals. 

Group details last updated July 2015.

Talk to other families about your child's condition

Visit our online Wolfram syndrome group

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