Providing information for patients and professionals on research and clinical care in genetic types of diabetes.

Diabetes Insipidus and Mellitus with Optic Atrophy and Deafness (DIDMOAD)

(also known as Wolfram Syndrome)

A syndrome involving Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (DIDMOAD) is recessively inherited and results from a mutation in the transmembrane gene, WFS1. Presentation is usually in the first decade, with insulin dependent diabetes and optic atrophy. Diabetes insipidus and sensorineural deafness occur in the second decade, renal tract outflow problems in the third, and multiple neurological problems (including ataxia) in the fourth. Death usually follows respiratory failure due to brain stem atrophy, and few patients live beyond middle age.


GENETIC TESTING IN WOLFRAM SYNDROME

The diagnosis of Wolfram syndrome is clinical, based on the combination of childhood onset diabetes mellitus and progressive optic atrophy. In some circumstances genetic testing can be useful, provided it is offered in conjunction with professional genetic counselling. We directly sequenced the WFS1 gene in 19 families with Wolfram syndrome, and found nonsense, frameshift and deletion mutations in 17 families (Hardy et al, 1999). We have since piloted a genetic testing service, offering screening of exon 8 of the WFS1 gene. This is the largest exon, and our studies have shown that 90% of mutations are located within this exon. We estimate that screening exon 8 in patients who fulfill the clinical criteria will identify at least 1 disease causing mutation in 85% of patients. For further details, please contact:

Dr Tim Barrett
Children Nationwide Senior Lecturer Paediatrics
Diabetes Unit
Birmingham Children’s Hospital
Steelhouse Lane
Birmingham
B4 6NH

Email: T.G.Barrett@bham.ac.uk

Hardy H, Khanim F, Torres R, Scott-Brown M, Sellar A, Poulton J, Collier D, Kirk J, Polymeropoulos M, Latif F, Barrett T. Mutation analysis and preliminary genotype/phenotype analysis in 19 Wolfram syndrome (DIDMOAD) kindreds (Am J Hum Genet 1999;65:1279-1290)