Familial Partial Lipodystrophy Presenting as Extreme Hypertriglyceridemia and Acute Pancreatitis

A 40-year-old white female presented with recurrent acute pancreatitis due to extreme hypertriglyceridemia. She developed diabetes mellitus at age 38 years, but despite 195 units of insulin daily, it was not well controlled. She was also on gemfibrozil 600 mg twice daily orally. Her body mass index was 23.6 kg/m², and she had a well-built, muscular appearance; round face; and double chin. She had acanthosis nigricans and hepatosplenomegaly. She had marked loss of subcutaneous (SC) fat from both the upper and lower extremities and from the gluteal region with prominent muscles and subcutaneous veins. Her triceps skinfold thickness was 5 mm and anterior mid-thigh skinfold thickness was 6 mm (both <10th percentile of normal values). Her older sister and older brother’s daughter also had diabetes mellitus and extreme hypertriglyceridemia. Her fasting blood glucose was 353 mg/dL, serum triglycerides were 14,100 mg/dL, and hemoglobin A1c was 9.1%. Genotyping for lamin A/C (LMNA) gene revealed a heterozygous c.1445G>A, p.Arg482Gln pathogenic variant establishing the diagnosis of familial partial lipodystrophy of Dunnigan variety (FPLD2). The case highlights that some patients with uncontrolled diabetes and extreme hypertriglyceridemia have underlying autosomal dominant FPLD2. The diagnosis of FPLD2 should be suspected in patients presenting with muscular appearance, acanthosis nigricans, Cushingoid appearance, diabetes mellitus requiring >200 units of insulin daily, polycystic ovarian syndrome, nonalcoholic hepatic steatosis, and severe hypertriglyceridemia. Since there are several genotypically distinct varieties of FPLD, genetic testing is required to establish the diagnosis.