SUN-LB012 Familial Partial Lipodystrophy Type 3: New Variant to the PPARG Gene Mutation

Abstract

Objective: Familial partial lipodystrophy (FPLD) syndromes are rare and characterized by variable loss of adipose tissue in some areas of the body with excess deposition of fat in other areas, and complex metabolic derangements. We present a patient who had a new pathogenic variant identified in the PPARG gene that causes familial partial lipodystrophy type 3. Clinical case: A 48-year old Caucasian female was referred to the Endocrinology department for management of her type 2 diabetes mellitus. Her glycated hemoglobin was 12.1% and triglycerides were 2343 mg/dl. She was diagnosed with type 2 diabetes mellitus in the third decade of life. The patient had extreme insulin resistance with diabetic triopathy. She had a history of severe hypertriglyceridemia that lead to 3 episodes of pancreatitis. Family history was significant for hypertriglyceridemia in her father and a paternal uncle, both of whom died of hemorrhagic pancreatitis. Examination revealed a cushingoid appearance with facial, neck and truncal obesity and loss of peripheral fat on the buttocks, thighs and forearms. Her gastrocnemii appeared prominent. She had normal thyroid function and a normal 1 mg dexamethasone suppression test. Genetic testing revealed a new pathogenic heterozygous variant in the PPARG gene (c.1164del) that produces a premature stop codon (consistent with FPLD type 3). The patient was treated with Insulin Glargine-U300, Aspart and Pioglitazone. Three months after diagnosis, the patient passed away from myocardial infarction. Discussion: FPLD type 3 is a very rare type of autosomal dominant FPLD, reported in about 30 individuals worldwide per National Organization for Rare Disorders (NORD). It is resulted from mutation of PPARG gene, which encodes PPAR-gamma nuclear transcription factor. PPAR-gamma is a regulator of adipocyte differentiation. Loss of PPARG function leads to peripheral fat loss which primarily involves the gluteal region, calves and forearms with deposition of fat on the face, neck, and truncal areas. Metabolic complications include hypertriglyceridemia, insulin resistant diabetes, hypertension, hepatic steatosis, and pancreatitis. Management includes a calorie-restricted diet, exercise and pharmacotherapy. Conclusion: Recognition of the clinical features of FPLD including atypical fat distribution, hypertriglyceridemia, recurrent pancreatitis and severe insulin resistance can lead to early diagnosis and intervention which may reduce mortality in FPLD patients. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.