Familial hyperinsulinism

Familial hyperinsulinism (also known as congenital hyperinsulinism, persistent hyperinsulinemic hypoglycemia of infancy, or nesidioblastosis) is a group of rare genetic disorders characterized by inappropriate and excessive secretion of insulin from the pancreatic beta cells, leading to persistent and recurrent episodes of hypoglycemia (low blood sugar). This condition primarily affects the endocrine system, specifically the pancreas, but the resulting hypoglycemia can have severe consequences for the central nervous system, potentially causing seizures, intellectual disability, and permanent brain damage if not promptly recognized and treated. The disease most commonly presents in the neonatal or infantile period, though milder forms may present later in childhood or even adulthood. Key symptoms include lethargy, poor feeding, irritability, seizures, and episodes of loss of consciousness related to low blood glucose levels. Affected infants often have high birth weight (macrosomia) due to the anabolic effects of excess insulin during fetal development. The severity of hypoglycemia varies widely, ranging from mild forms responsive to dietary management to severe forms requiring aggressive medical or surgical intervention. Multiple genetic subtypes have been identified, with mutations in genes regulating insulin secretion from beta cells, including ABCC8 and KCNJ11 (encoding the components of the ATP-sensitive potassium channel), GCK, GLUD1, HADH, HNF4A, HNF1A, SLC16A1, and UCP2, among others. Treatment options include frequent feeding with glucose-enriched formulas, the medication diazoxide (which suppresses insulin release), octreotide (a somatostatin analog), and in medically unresponsive cases, partial or near-total pancreatectomy. Focal forms of the disease, where only a localized region of the pancreas is affected, can often be cured by limited surgical resection, making the distinction between focal and diffuse disease critically important for management. Advances in 18F-DOPA PET scanning have significantly improved the ability to identify focal lesions preoperatively.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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