DIDMOAD syndrome: a family with three affected siblings.

In 1938 Wolfram reported the occurrence of diabetes mellitus and optic atrophy in four of eight sibs.' Over 100 similar cases have since been reported and several other clinical features have been described.2 3,4 The genetic disorder is commonly known as DIDMOAD syndrome, the mnemonic for Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness. This report describes three siblings with this syndrome in a family of ten born to healthy non * consanguineous parents. The family has been briefly referenced in McKusick's catalogue of Mendelian inheritance in man.5 CASE 1 (MG). A female born in 1959, presented with symptoms of diabetes mellitus at the age of eight. At that time she had diminished vision (N/34), deafness, and was considered to be educationally subnormal although attending a school for the deaf and blind. Ophthalmological examination revealed rotary nystagmus, a left convergent squint, early cortical cataracts and bilateral primary optic atrophy. She was treated with insulin, and during the next seven years she had frequent hospital admissions with hypo-or hyperglycaemic states. The coexistence of diabetes insipidus became apparent in 1974 at age 15, and polyuria was controlled with oral chlorpropamide. The same year she had to be admitted for long term care in a hospital for special care, due to behavioural problems. In 1975 she aspirated while eating, and required intensive resuscitation with artificial ventilation for ten days. While unconscious her serum osmolality remained normal without chlorpropamide, but on regaining consciousness poly-dipsia and polyuria recurred, the urine osmolality fell to 230 mosm/l and serum osmolality rose to 316 mosm/l. On recommencing chlorpropamide the serum osmolality improved to 304 mosm/l and urine osmolality to 762 mosm/l. Hypertonic saline infusion test was unsuccessful due to poor patient cooperation. Her other abnormalities included high tone deafness, bilateral hydronephrosis and hydroureters and incomplete emptying of the bladder. At the age of 19 she developed grand mal seizures. EEG showed non-specific abnormalities. In 1982 she aspirated again while eating and died.