MON-045 A Case of Familial Partial Lipodystrophy Type 2 With Isolated Hepatic Steatosis

Abstract E. Tirthani: None. R.D. Siegel: None. Background: Familial partial lipodystrophy type 2 (FPLD2) or “Dunnigan lipodystrophy” is a rare autosomal dominant disease caused by pathogenic variants in the LMNA gene. Patients with FPLD2 generally present with multiple complications from adipose tissue dysfunction and insulin resistance, including diabetes mellitus (DM), cardiovascular disease (CVD), hypertension (HTN), hypertriglyceridemia, hyperandrogenism, and infertility. We describe a unique case of FPLD2 with isolated hepatic steatosis without any other clinical or biochemical evidence of metabolic syndrome. Clinical Case: A 38-year-old female was referred to endocrinology due to concerns about her appearance. The patient noted a change in body composition in her early 20s with increased fat deposition over her face and neck and thin arms and legs. She denied a history of DM, HTN, CVD, pancreatitis, irregular menses, or family members with known lipodystrophy. Given her “Cushingoid appearance,” a 1 mg dexamethasone suppression test was done in the past which was normal. Her blood pressure at the office visit was 112/82 mmHg, with a BMI of 20.47 kg/m². On physical examination, the patient was found to have increased facial and supraclavicular fat deposition, a lack of subcutaneous fat in the upper and lower extremities, prominent muscles, superficial veins, and a scaphoid abdomen. She did not have hirsutism, skin tags, or acanthosis nigricans. Fasting labs showed blood glucose 82 mg/dL, insulin 6.2 uIU/mL (2.6-24.9 uIU/mL), leptin 3.6 ng/mL (2.4-13.4 ng/mL for BMI of 20), HbA1c 5.2%, triglycerides 60 mg/dl, LDL(c) 135 mg/dL, HDL 45 mg/dL, LH 1.9 mIU/mL, FSH 5.5 mIU/mL, estradiol 68 pg/mL, total testosterone 10 ng/dL, free testosterone 0.6 ng/dL, ALT 8 U/L, and AST 15 U/L. With the lack of a family history of lipodystrophy and the absence of clinical signs and labs suggestive of metabolic syndrome, the diagnosis of FPLD was questioned. Biochemical testing to look for causes of acquired partial lipodystrophy, including HIV, rheumatologic disease, pernicious anemia, Hashimoto’s disease, glomerulonephritis, and celiac disease was performed but was normal. Finally, genetic testing was pursued, which showed a c.1445 G>A p.(R482Q) pathogenic variant in the LMNA gene, confirming the diagnosis of FPLD2. While assessing for liver disease due to FLPD2, a FibroScan showed moderate steatosis (S2: 260 to 290 dB/m) but mild liver fibrosis (F1: 5.48-8.29 kPa). The patient was started on pioglitazone to treat hepatic steatosis and possibly increase subcutaneous peripheral fat deposition. Conclusion: Patients with FPLD2 may present with a spectrum of metabolic abnormalities. The patient presented here had a lipodystrophy phenotype with isolated hepatic steatosis without laboratory derangements suggestive of insulin resistance and metabolic syndrome. Pioglitazone may help to treat hepatic steatosis in partial lipodystrophy. Monday, June 3, 2024