Abstract
INTRODUCTION: Congenital hyperinsulinism (CHI) is a heterogeneous disorder of insulin dysregulation, leading to hypoglycemia. This study describes the clinical characteristics, genetics, and management of CHI in Argentina. METHODS: We retrospectively reviewed 70 probands diagnosed with CHI (2008-2021) at multiple centres across Argentina. Clinical, biochemical, imaging, and treatment data were analyzed. Genetic testing was performed in 49 probands using Sanger and targeted next-generation sequencing of CHI-related genes. RESULTS: Transient CHI was identified in 23/70 (33%) probands, with a median duration of 2 months. Risk factors for perinatal stress-induced hyperinsulinism (PSHI) were present in 85% of transient cases. Persistent CHI was diagnosed in 44/70 (63%) individuals, of whom 31 responded to diazoxide. Late-onset CHI (diagnosed >3 years) was identified in 3 children. A pathogenic variant was detected in 19/49 (39%) probands, all had persistent CHI. ABCC8 variants were most common accounting for 68% (13/19) of diagnoses. Imaging in 17 cases revealed focal disease in 8, diffuse disease in 8, and atypical disease in 1 individual. Seven individuals with focal disease underwent lesionectomy, which was curative in 5 (71%). Three children with diffuse disease required near-total pancreatectomy, with one developing postoperative diabetes. CONCLUSIONS: This study provides the largest CHI cohort reported from South America and highlights the clinical and genetic heterogeneity of the condition. Transient CHI was often associated with PSHI risk factors, while persistent CHI was predominantly linked to K-ATP channel variants. The findings underscore the importance of genetics and imaging for CHI management and emphasize the need for increased access to molecular diagnostics.