Hyperinsulinemic Hypoglycemia of Infancy due to Novel HADH Mutation in Two Siblings

Background: Hyperinsulinemia is the commonest cause of persistent hypoglycemia in infancy. Inactivating mutations in the genes ABCC8 and KCNJ11 are the commonest cause. Mutation in the HADH gene, which encodes the short-chain-L-3-hydroxyacyl-CoA dehydrogenase, is a rare cause. Case characteristics: Two Indian sisters who presented with hyperinsulinemic hypoglycemia of infancy. Observation/Intervention: A novel homozygous missense mutation in the HADH gene was identified in both the sisters, while the parents were found to be heterozygous carriers. Outcome: Establishment of molecular diagnosis, optimization of therapy and counseling of parents regarding risk of recurrence in future pregnancy. Messages: HADH mutations are rare causes of hypoglycemia and can be mitigated with diazoxide and appropriate dietary therapy if identified early.