Congenital isolated hyperinsulinism arises from dysregulation of insulin secretion by pancreatic beta cells. No causative genes are certified in this packet. Recognized disease subtypes include both diffuse and familial forms, and disease presentations are distinguished clinically by response to diazoxide therapy.

Diagnosis is established by documenting insulin secretion inappropriate to blood glucose concentrations during hypoglycemic episodes in the neonatal or early infantile period. Classification into diazoxide-sensitive or diazoxide-resistant forms is a key step in clinical characterization. Fluorodopa F 18 PET imaging is under investigation for localizing focal forms of the condition.

No FDA-approved treatments for congenital isolated hyperinsulinism are certified in this packet. Several investigational agents hold FDA orphan drug designation, including glucagon analogs and a fully human IgG2 monoclonal antibody targeting insulin receptors — all under development and not approved for therapeutic use. A fluorodopa F 18 diagnostic agent also holds orphan designation. Clinical management focuses on correcting and preventing hypoglycemia to reduce neurological risk.

Natural history and prognosis data are not certified in this packet. The disease definition states that recurrent profound hypoglycemia requires rapid and intensive treatment to prevent neurological sequelae.

Certified active trials include Phase 3 studies of dasiglucagon (NCT03941236) and RZ358 (NCT06208215), Phase 2 and 3 imaging studies of 18F-DOPA PET for focal CHI localization (NCT04205604; NCT04706910), a Phase 2 trial of efpegerglucagon/HM15136 (NCT04732416), and a Phase 1 imaging study (NCT02021604). The published research landscape encompasses 168 classified articles, with case reports and case series the largest category.