Evaluation of insulin resistant diabetes mellitus in Alström syndrome: a long-term prospective follow-up of three siblings

Alström syndrome is a rare cause of diabetes mellitus. We studied two generations of a Turkish family in whom four members were affected by Alström syndrome. The natural course of the syndrome in three sisters was followed for 13 yr. The three sisters had short stature and truncal obesity, and developed complete blindness due to retinitis pigmentosa at 10, 5 and 13 yr of age. Two had sensorineural hearing loss and mild mental retardation, while the other developed diabetic ketoacidosis (DKA) at 14 yr and was treated with insulin from onset of diabetes. In the second case, diagnosis of diabetes was made by an OGTT at age 20 yr, and controlled with diet alone for 11 yr, then with a sulphonylurea for 2.5 yr, then with insulin. The third case developed acute hyperglycaemia at 20 yr, and required insulin from onset. Moreover, transitional features of impaired carbohydrate and fat metabolism (severe hyperinsulinaemia and insulin resistance progressing to islet β cell failure, and hypertriglyceridaemia with fatty liver) were demonstrated, in accord with the literature. Previously unreported findings characteristic of nephro-uropathy with early-onset hypertension were also detected, and included in all cases proteinuria, glomerulopathy, and abnormal locations of the kidneys, narrowed uretero–renal junctions and dilated ureters.