Background Congenital lipodystrophy is an exceedingly rare genetic disorder with an estimated worldwide prevalence of less than 1 case per million individuals. Four distinct genetic mutations underlie congenital lipodystrophy, including AGPAT2, BSCL2, CAV1, and PTRF genes. This condition is Characterized by the near absence of subcutaneous adipose tissue, resulting in fat deposition in internal organs such as the liver. It leads to cirrhosis and metabolic disturbances, including hypertriglyceridemia and insulin resistance, often precipitating early-onset diabetes mellitus. We report a case of congenital lipodystrophy with a focus on the management of severe diabetes with insulin resistance.

Case Report(s) Our patient is a 14-year-old female with congenital lipodystrophy, initially manifesting as hypertriglyceridemia with normal blood glucose levels. Subsequently, at 14 years of age she experienced irregular menstrual periods and worsening acanthosis nigricans. Continuous glucose monitoring over two weeks revealed consistently elevated fasting and postprandial blood glucose readings. Physical examination demonstrated a muscular appearance, generalized lipoatrophy, enlarged hands and feet, hirsutism, and prominent acanthosis nigricans on the neck and flexor folds. Laboratory findings indicated an elevated hemoglobin A1c of 7.7% and hypertriglyceridemia.

Treatment was initiated with insulin, metformin, and dietary modifications, eventually necessitating high insulin doses, including insulin Lantus (60 Units daily) and insulin Lispro (35 Units with meals thrice daily). Subsequently, metreleptin therapy was introduced, resulting in improved glycemic control, with blood glucose levels stabilizing between 70 and 150 mg/dl, allowing for the discontinuation of insulin therapy.

Conclusion(s) Congenital lipodystrophy poses a rare and complex challenge, often complicated by severe diabetes due to insulin resistance. Metreleptin emerges as an effective therapeutic option for managing diabetes in these patients. As a recombinant analog of the human hormone leptin, metreleptin offers promising outcomes in glycemic control and warrants consideration in the management of congenital lipodystrophy-related diabetes.