Six Chinese children with type 2 congenital generalized lipodystrophy: clinical features and follow-up

Background Congenital generalized lipodystrophy type 2 (CGL2) is a rare autosomal recessive disorder characterized by the near-total absence of adipose tissue from birth, severe insulin resistance, and other metabolic abnormalities. This study analyzed the clinical and genetic characteristics of six Chinese pediatric patients with CGL2 over a 10-year period. Methods Six children diagnosed with CGL2 underwent clinical evaluations, including medical histories, physical examinations, and metabolic assessments. Genetic testing was carried out using whole-exome sequencing and Sanger sequencing to identify mutations of the BSCL2 gene. Follow-up data were collected over 10 years to assess the natural progression of the disease. Results All six patients presented with typical CGL2 features, including a generalized lack of adipose tissue, acanthosis nigricans, hepatomegaly, and severe hypertriglyceridemia. Genetic analysis confirmed pathogenic variants of the BSCL2 gene in all patients, including previously reported and novel mutations. Long-term follow-up revealed progressive complications, such as diabetes mellitus, and hepatic steatosis, highlighting the chronic and debilitating nature of this disease. Conclusion The natural history of CGL2 in these six Chinese children highlighted the severe and progressive nature of the disorder. Genetic testing was indispensable for its diagnosis and family counseling. Early and continuous multidisciplinary management is crucial to improve the outcomes and quality of life for patients with CGL2.