Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by the near-total loss of subcutaneous adipose tissue soon after birth, resulting in ectopic fat deposition and severe metabolic disturbances. Most cases are caused by or gene mutations. We aimed to report two unrelated CGL patients with a novel frameshift mutation in (p.Leu124Serfs*26).
Clinical features and laboratory were obtained by medical interview and medical records review. DNA was extracted, amplified and sequenced. Mutation Taster was used to estimate the potential biological impact of the mutations on the protein function.
Patient 1: a 30-year-old woman with lipodystrophy phenotype at birth and diagnosis of diabetes at age 13 presented with severe hypertriglyceridemia and pancreatitis at age 17, hypertension and albuminuria at age 18, proliferative diabetic retinopathy with visual loss at age 25, and an acute myocardial infarction due to multivessel coronary disease during a hospitalization for forefoot amputation at age 29. At this time, she required hemodialysis due to end-stage renal disease. Patient 2: a 12-year-old girl with lipodystrophy phenotype and hypertriglyceridemia detected in the first year of life and abnormalities in the global longitudinal strain, evaluated by speckle-tracking echocardiography last year. Molecular analysis identified a c.369_372delGCTC (p.Leu124Serfs*26) mutation in both unrelated patients, a compound heterozygous mutation in Patient 1, and homozygous mutation in Patient 2.
We describe two unrelated patients with type 1 CGL due to Leu124Serfs*26, a novel frameshift mutation, presenting as early cardiovascular disease. These findings suggest an association between Leu124Serfs*26 and a more aggressive phenotype.

© The Author(s) 2020.