CSEM2404 - CSEM Resident Oral Abstract Presentations - A Novel PPARG Pathogenic Frameshift Variant in Familial Partial Lipodystrophy: A Case Report

Abstract:

Introduction: Lipodystrophies are a group of rare disorders characterized by a lack or maldistribution of adipose tissue. These disorders are associated with many complications including hypertriglyceridemia, pancreatitis, diabetes mellitus, and atherosclerotic cardiovascular disease. Familial partial lipodystrophy type 3 (FPLD3) is a rare type of lipodystrophy associated with pathogenic PPARG variants. PPARG encodes peroxisome proliferator-activated receptor gamma, which is the master regulator of adipogenesis. This case report describes a patient with FPLD3 possessing a novel PPARG pathogenic variant.

Case Presentation: A 32-year-old woman with a remote history of acute pancreatitis presented with triglyceride levels as high as 19.3 mmol/L during late pregnancy. She was started on fenofibrate which lowered her triglycerides to 12.7 mmol/L. Furthermore, she was diagnosed with gestational diabetes, requiring multiple daily injections of insulin. Given significantly elevated fasting blood glucose levels in pregnancy and a low-normal pre-pregnancy body mass index, she underwent genetic testing for maturity onset diabetes of the young (MODY), which did not reveal any MODY variants. It did however identify a heterozygous, likely pathogenic frameshift variant in PPARG (Glu323Glufs*15), not previously described. Her genetic analysis also demonstrated a high triglyceride polygenic risk score in the 82nd percentile. Post-partum, fenofibrate was discontinued due to patient preference while breastfeeding, with a most recent triglyceride level of 3.1 mmol/L.

Conclusion: A case of FPLD3 with a novel, pathogenic frameshift variant in PPARG is described. This patient’s genetic analysis and clinical course will aid in further understanding of FPLD3 and the genotype-phenotype relationships related to the identified PPARG variant.