Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by generalized absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatomegaly, hepatic steatosis, and early onset of diabetes. Herein, we described a case with CGL2 due to novel homozygous BSCL2 gene mutation.
Three years-seven months old girl presented with a general lack of subcutaneous fat, prominent muscular hypertrophy, hollow cheeks, triangular face, acanthosis nigricans in fold areas, especially in the neck-bilateral axilla, hypertrichosis in arms-legs, abdominal swelling due to hepatomegaly, which are characteristic physical findings of CGL. Her parents were first-degree cousins. In laboratory: Glucose 75 mg/dL (70-105), C-peptide 6.8 ng/mL (0.9-4.3), insulin 47.4 µIU/mL (1.9-23), HbA1c 5.2% (4.8-6.0), total cholesterol 132 mg/dL (<200), and triglyceride 134 mg/dL (<200). Hyper triglyceridemia was firstly detected at 5 years of age with metformin therapy. Despite taking metformin treatment, the patient’s insulin levels increased steadily, and serum AST levels were also elevated. At the age of nine, grade 2 hepatic steatosis with hepatomegaly was detected in ultrasonography.
During follow-up, her HbA1c level has increased to 6.5% at the age of eleven years and three months. The fasting and 2-hour post-OGTT glucose-insulin levels of the patient were 152 mg/dL-158.3 µIU/mL and 209 mg/dL-95.8 µIU/mL, respectively. Insulin detemir was started in addition to metformin treatment because of diagnosis diabetes.
A clinical diagnosis of CGL was corrected by the identification of a novel homozygous mutation (IVS2+2 T>C) in the BSCL2 gene. Analyzes with GenSplicer and Human Splicing Finder modeling programs show that this mutation can cause the disease.