PSUN81 A novel case of congenital generalized lipodystrophy (CGL) with no genetic abnormalites in the AGPAT2, BSCL2, CAV1, and CAVIN1 genes.

Abstract

Abstract Congenital generalized lipodystrophy (CGL) is a genetic disorder charaterized by total body fat loss. The extent of fat loss is usually associated with the severity of the disease and patients typically develop metabolic complications such as hypertriglyceridemia, hepatic steatosis, insulin resistance, and diabetes mellitus. Mutations in the AGPAT2, BSCL2, CAV1, and CAVIN1 genes are known to cause CGL. We report a new case of CGL but where no genetic aetiology has yet been identified in the known genes that cause CGL. The patient is a female child born at 36 weeks gestation with a birth weight os 2.57 kg. Soon after birth she was diagnosed clinically with CGL with both the DEXA and MRI scans showing severely diminished adipose tissue and 0% body fat respectively. She had severe failure to thive and developed diabetes mellitus, hyperlipidaemia, hypertrophic cardiomyopathy, severe scalp seborrheic dermatitis and hepatic steotosis. At 2 years of age her weight was only 3.7kg and she died from an upper respiratory tract infection. Whole exome sequencing and trio analysis did not find any mutations or copy number variants (CNV) in the AGPAT2, BSCL2, CAV1, and CAVIN1 genes associated with CGL. De-novo variants were found in the genes PCNT, PDE4DIP and STAT3 which need further functional validation. This case suggests that other possibly novel genetic mechanisms may be responsible for the CGL observed in this patient. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.