Genotype - phenotype correlation in an adolescent girl with pathogenic variant in PPARƴ gene causing severe hypertriglyceridemia and early onset type 2 diabetes.

Severe hypertriglyceridemia (HTG) (>885 mg/dl) can be caused by familial partial lipodystrophy Type 3 (FPLD 3), an autosomal dominant disorder caused by a loss of function of the peroxisome proliferator activated receptor gamma (PPARG), characterized by abnormal distribution of fat and metabolic derangements. A 16-year-old female (body mass index, BMI 23.5 kg/m2) was hospitalized twice for pancreatitis (TG level >2200 mg/dl). She was managed with bowel rest, insulin infusion, and plasmapheresis. On a low fat 10 g daily diet and fenofibrate 160 mg daily her fasting TG had decreased to 411 mg/dL (range 0-149). She had a normal leptin level. Panel testing of genes involved in triglyceride metabolism revealed a known pathogenic variant in PPARG gene (c.452A>G p.Tyr151Cys). A second variant detected in this gene, c.1003G>C (p.Val335Leu), is considered benign. HbA1C of 6.6% and two-hours oral glucose tolerance test confirmed Type 2 diabetes (T2DM). We outline the earliest description of T2DM in an adolescent with a pathogenic variant of PPARG. PPARG related FLPD 3 should be considered in lean children presenting with severe HTG and insulin resistance and treatment with PPARy agonists Thiazolidinediones should be considered.