Familial Lipoatrophic Diabetes with Dominant TransmissionA NEW SYNDROME1

Several members of two families were found to have an unusual form of lipoatrophy extending over three generations. The propositus of the first family, a girl of 19 years, showed symmetrical lipoatrophy of the trunk and limbs with a rounded, full face, tubero-eruptive xanthomata, acanthosis nigricans, insulin-resistant diabetes and Type V hyperlipidaemia. Her mother and maternal aunt showed symmetrical lipoatrophy, sparing the face, and diabetes mellitus. The latter also exhibited acanthosis nigricans and Type V hyperlipidaemia. The grandmother and maternal great-aunt of the propositus were said to have had a similar form of lipoatrophy, but were not known to be diabetic. The propositus of the second family, a woman of 49 years, also showed symmetrical lipoatrophy of the trunk and limbs with a rounded, Cushingoid face. Laboratory investigations revealed mild Type V hyperlipidaemia, chemical diabetes, and high plasma insulin levels. The mother, grandmother, and three second cousins of the propositus were reported to have been similarly affected by lipoatrophy, but were not known to be diabetic. The syndrome of lipoatrophy, diabetes, and hyperlipidaemia found in the two families appears clinically and genetically distinct from those of acquired lipoatrophic diabetes, congenital total lipodystrophy, and progressive partial lipodystrophy and has not been hitherto described. Thepattern of inheritance is consistent with autosomal dominant transmission with variable expressivity. The geographical origins of the lipoatrophic trait in the nearby towns of Dingwall and Inverness suggest a common genetic source for the syndrome in the north of Scotland.