Congenital generalized lipodystrophic diabetes(CGLD) is a rare form of diabetes caused by the genetic defects affecting insulin action. This article describes two cases of CGLD within a family. The patients, siblings, exhibited systemic fat atrophy, severe hypertriglyceridemia, insulin resistance and hepatomegaly. Genetic analysis revealed a shared homozygous nonsense mutations in the BSCL2 gene c. 757G>T: p.E253*. Case 1(elder brother) presented with more severe hypertriglyceridemia, pronounced microvascular complications of diabetes, and abnormalities in bone metabolism. In contrast, Case 2(younger brother) demonstrated lower body fat content and reduced limb muscle strength. Despite sharing the same pathogenic mutation, the siblings displayed notable differences in clinical presentation, underscoring the phenotypic heterogeneity of CGLD. These findings highlight the importance of recognizing variable clinical manifestations in CGLD. Endocrinologists should consider this heterogeneity to ensure accurate diagnosis and tailored treatment strategies for affected individuals.

Congenital generalized lipodystrophic diabetes(CGLD) is a rare form of diabetes caused by the genetic defects affecting insulin action. This article describes two cases of CGLD within a family. The patients, siblings, exhibited systemic fat atrophy, severe hypertriglyceridemia, insulin resistance and hepatomegaly. Genetic analysis revealed a shared homozygous nonsense mutations in the BSCL2 gene c. 757G>T: p.E253*. Case 1(elder brother) presented with more severe hypertriglyceridemia, pronounced microvascular complications of diabetes, and abnormalities in bone metabolism. In contrast, Case 2(younger brother) demonstrated lower body fat content and reduced limb muscle strength. Despite sharing the same pathogenic mutation, the siblings displayed notable differences in clinical presentation, underscoring the phenotypic heterogeneity of CGLD. These findings highlight the importance of recognizing variable clinical manifestations in CGLD. Endocrinologists should consider this heterogeneity to ensure accurate diagnosis and tailored treatment strategies for affected individuals.