CHARGE症候群および病原性CHD7バリアントを有する個人の先天性高インスリン血症

Hyperinsulinemic hypoglycemia (HI) is a rare feature in individuals with coloboma, heart defects, atresia choanae, retardation of growth and development, genital abnormalities, and ear abnormalities (CHARGE) syndrome, though its underlying mechanisms remain poorly understood. We report a Chilean female proband with genetically confirmed CHARGE syndrome caused by a pathogenic variant in the CHD7 gene, who presented with HI in the neonatal period. Initial hypoglycemia was detected on days 2-3 of life, followed by recurrent episodes prompting biochemical investigation. On day 21, HI was biochemically confirmed. Comprehensive hormonal evaluation, including cortisol and growth hormone testing, excluded deficiencies in these hormones as contributing factors. Genetic screening of 22 known HI-associated genes revealed no pathogenic variants, supporting the hypothesis that HI in this case is related to CHARGE syndrome rather than being a coincidental finding. The patient responded well to diazoxide treatment, which allowed for maintenance of normoglycemia, with gradual dose reduction as glucose management normalized. This case, along with 2 previously reported cases, suggests that HI can be an integral part of CHARGE syndrome. Further research is needed to understand the mechanisms connecting CHD7 variants and HI and to refine management strategies for affected individuals.