Genetic characteristics of patients with congenital hyperinsulinism.

TitleGenetic characteristics of patients with congenital hyperinsulinism.
Publication TypeJournal Article
Year of Publication2018
AuthorsVajravelu MEllen, De León DD
JournalCurr Opin Pediatr
Date Published2018 08
KeywordsChild, Congenital Hyperinsulinism, Genetic Markers, Genetic Testing, Humans, Infant, Syndrome

PURPOSE OF REVIEW: Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infants and children. Early and appropriate recognition and treatment of hypoglycemia is vital to minimize neurocognitive impairment.

RECENT FINDINGS: There are at least 11 known monogenic forms of hyperinsulinism and several associated syndromes. Molecular diagnosis allows for prediction of the effectiveness of diazoxide and the likelihood of focal hyperinsulinism. Inactivating mutations in the genes encoding the ATP-sensitive potassium channel (KATP hyperinsulinism) account for 60% of all identifiable mutations, including 85% of diazoxide-unresponsive cases. Syndromes or disorders associated with hyperinsulinism include Beckwith-Wiedemann syndrome, Kabuki syndrome, Turner syndrome, and congenital disorders of glycosylation. Although focal hyperinsulinism can be cured by resection of the lesion, therapeutic options for nonfocal hyperinsulinism remain limited and include diazoxide, octreotide, long-acting somatostatin analogs, and near-total pancreatectomy. Although sirolimus has been reported to improve glycemic control in infants with diazoxide-unresponsive hyperinsulinism, the extent of improvement has been limited, and significant adverse events have been reported.

SUMMARY: Identification of the cause of congenital hyperinsulinism helps guide management decisions. Use of therapies with limited benefit and significant potential risks should be avoided.

Alternate JournalCurr. Opin. Pediatr.
PubMed ID29750770
PubMed Central IDPMC6084463
Grant ListR01 DK098517 / DK / NIDDK NIH HHS / United States
T32 DK007314 / DK / NIDDK NIH HHS / United States