Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1

摘要

Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder, characterized by dysregulated insulin secretion. Pathogenic variants in at least twelve different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, HNF1A, UCP2, TRMT10A HK1, and PGM1) are known to cause CHI. Pathogenic variants in the GLUD1 gene, which encodes the enzyme glutamate dehydrogenase (GDH), account for 5% of the cases of congenital hyperinsulinemic hypoglycemia. Pathogenic variants in GLUD1 typically present in late infancy, are diet and/or diazoxide-responsive and cause protein-induced hyperinsulinemic hypoglycemia as insulin secretion is triggered by allosteric activation of GDH by leucine. The authors are presenting three unrelated Indian children, who manifested with fasting as well as dietary protein induced hypoglycemia in late infancy, and were diagnosed to have hyperinsulinemic hyperammonemic hypoglycemia due to pathogenic variants in GLUD1. Although the hypoglycemia responded to diazoxide, delayed diagnosis and irregular treatment had resulted in neurological problems in two of the three children. Early identification, appropriate dietary modifications and regular treatment with diazoxide can prevent adverse neurological outcome.