Wilson, DonTorre, AlejandroBrautbar, ArielHamilton, Luke2019-08-222019-08-222016-03-232016-03-02https://hdl.handle.net/20.500.12503/26750Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near total absence of body fat from birth, with predisposition to insulin resistance, diabetes, hypertriglyceridemia and hepatic steatosis.1 This clustering of risk factors is often associated with increased atherogenic cholesterol, increasing risk of premature atherosclerotic cardiovascular disease (ASCVD)-related events. We describe two Mexican-American siblings, a 17 yr old male and a 6 yr old female, with congenital generalized lipodystrophy type 4, a variant of CGL, due to null mutations in polymerase I and transcript release factor (PTRF).1 Both siblings had characteristic findings of near lack of total body fat with very low levels of serum leptin, insulin resistance, hepatic steatosis, dyslipidemia and myopathy with elevated CPK. Leptin (ref range 1.4-16.5): 0.8 ng/mL. Measurement of fasting lipid and lipoproteins revealed severe hypertriglyceridemia and low HDL-C. Elevated levels of atherogenic cholesterol (non-HDL-C and LDL-C) are causally related to the development of atherosclerosis, the key underlying process contributing to most clinical ASCVD events. Measurements of atherogenic cholesterol in our two siblings with CGL-4, appeared to increase with age. Lipid profiles in children with CGL-4 are similar to those described in metabolic syndrome, i.e. moderate to severe hypertriglyceridemia with low HDL-C and increased small dense LDL-C. Although CVD risk is increased, children with CGL-4 are prone to sudden cardiac death, the latter most likely a result of the cardiomyocyte dysfunction.application/pdfenposter