Sindrome progeroide atipica con lipodistrofia parziale familiare, dovuta alla mutazione missenso c.1045 C > T (p.Arg349Trp) in eterozigosi del gene LMNA, e diabete mellito di tipo 2

Atypical progeroid syndrome with familial partial lipodystrophy due to a missense c.1045 C > T (p.Arg349Trp) in heterozygous LMNA mutation and type 2 diabetes mellitus

Familial partial lipodystrophy (FPLD) associated with LMNA gene mutations is a rare form of lipodystrophy disorder characterized by partial absence of subcutaneous adipose tissue and predisposition to develop metabolic complications related to insulin-resistance inclu-ding type 2 diabetes mellitus (T2D). Recently, this peculiar phenotype has been associated to atypical progeroid syndrome (APS). We present a case of 31-year-old woman with progeria features, partial lipodystrophy, type 2 diabetes mellitus (T2D), hypertriglyceridemia and hepatic steatosis. The baseline insulin sensitivity and secretion assessment showed strong insulin-resistance with hyperglycemia and elevated insulin secretion. Genetic analysis revealed a missense heterozygous LMNA mutation c.1045 C > T (p. Arg349Trp) that established APS diagnosis with FPLD, so far studied and described in only 10 patients worldwide. The patient was initially treated with metformin, fenofibrate, omega-3 and low carb and low fat diet with optimal results on metabolic control related to glycemic and lipid profile; later, liraglutide (Glucagon-Like Peptide-1 analog, GLP-1) therapy was added. During the 6 month follow-up the anthropometric parameters improved, in particular a significant improvement in body composition with redistribution of fat mass and a reduction of visceral fat and liver volume were observed. The improvements obtained were consolidated and maintained in the following years. However, with disease progression, focal segmental glomerulosclerosis (FSGS) and peripheral neuropathy developed.
This case highlights the clinical and metabolic characteristics of this rare form of lipodystrophy and proposes an innovative therapeutic approach to manage the disease.