Endocrine Abstracts

Introduction: This study presents four clinical cases of lipodystrophies, which are a group of rare and heterogeneous diseases characterized by the decrease or lack of adipose tissue (AT) accompanied by metabolic complications.

Clinical cases: 1) 59-year-old woman with partial familial lipodystrophy, type 7 (OMIM #606721): Diagnosis of suspected type 1 diabetes (DM) at 28 (treated with insulin with poor control), class 1 obesity and hypertriglyceridemia. Objectively, absence of AT in the lower limbs, central obesity and accumulation of AT in the face and neck. Currently medicated with pioglitazone 15 mg, metformin/dapagliflozin 1000/5 mg twice daily, semaglutide 1 mg/weekly, atorvastatin 40 mg and ezetimibe 10 mg. HbA1c=7.2% and triglycerides(Tg)=134 mg/dl. 2) 27-year-old man with congenital generalized lipodystrophy - Berardinelli-Seip Syndrome: Generalized loss of AT in the 1st year of life. Comorbidities include DM diagnosis at 10, hypertriglyceridemia, hypoleptinemia (leptin<0.7 ng/ml), cirrhosis with portal hypertension, hypertrophic cardiomyopathy and hidradenitis suppurativa. Genetic study (GS) revealed a homozygous mutation in BSCL2. The patient is currently on metformin/empagliflozin 1000/5 mg twice daily, pioglitazone 30 mg and semaglutide 1 mg/weekly. HbA1c=6.0% and Tg=150 mg/dl. Metreleptin treatment was initiated in January 2024. 3) 19-year-old woman with acquired generalized lipodystrophy - Lawrence Syndrome: Clinical onset at 3 years. Comorbidities include Hashimoto’s thyroiditis, autoimmune hepatitis (AIH) with advanced fibrosis, autoimmune gastritis, hypertriglyceridemia, hypoleptinemia (leptin<0.05 ng/ml) and DM (diagnosed at 13 – treated with metformin, prandial and basal insulin). GS negative for AGPAT2, BSCL2, LMNA and PPARG. Positive anti-perilipin 1 antibodies. Metreleptin started in 2019, with improvements in hypertriglyceridemia and hepatosplenomegaly as well as remission of DM (HbA1c=5.1%). 4) 22-year-old woman with partial lipodystrophy: Central adiposity and absence of AT in the limbs identified at age 3. Comorbidities include AIH, neurodegenerative brain iron accumulation with congenital ataxia, insulin resistance (insulin=58 µU/ml; RR 2.6-24.9) and hypertriglyceridemia controlled with lifestyle measures (Tg=175 mg/dl). GS negative for AGPAT2 and LMNA - currently under evaluation in a medical genetic consultation.

Conclusion: Lipodystrophies exhibit diverse phenotypes, emphasizing the crucial role of physical examination in evaluating AT distribution. Early diagnosis allows a more appropriate treatment of both lipodystrophies and their metabolic complications.