Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a disorder characterized by dysregulation of insulin secretion and prolonged hypoglycemia. Mutations in the genes of both subunits of the β-cell KATP channel, Kir 6.2 (potassium channel) and SUR1 (sulfonylurea receptor) have been associated with the autosomal recessive form of this disorder. It was previously demonstrated that patients harboring SUR1 mutations often do not respond well to diazoxide. A patient is reported of compound heterozygosity for the 2 most common mutations previously reported to be associated with PHHI in Ashkenazi Jews; splice mutation of intron 32 (3993-9G→A) and deletion of phenylalanine at position 1388. Relatively low glucose utilization (<10 mg/kg/min) was needed to maintain blood glucose concentrations. In addition, treatment with diazoxide was highly effective. We suggest that diazoxide unresponsiveness is not always present in patients with SUR1 mutations and that the probable cause of the milder phenotype in this compound heterozygote state is the splice mutation.