Atypical Generalized Lipoatrophy and Severe Insulin Resistance due to a Heterozygous LMNA p.T101 Mutation

Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confirmed by DEXA (total body fat 8.6%). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identified a heterozygous substitution in exon 1 (c.29C > T) predicting a p.T101 mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.T101 mutation in LMNA gene. (Arq Bras Endocrinol Metab 2008; 52/8:1252-1256)