H01267 | |
H number | H01267 |
Name | Familial hyperinsulinemic hypoglycemia |
Description | Familial hyperinsulinemic hypoglycemia (HHF) is the most common cause of persistent hypoglycemia in infancy. Recent studies on the molecular basis of the disease have disclosed specific genetic defects in the regulation of insulin secretion. Seven different loci have been associated with hyperinsulinism: ABCC8, KCNJ11, HADHSC, GCK, GLUD1, SLC16A1, and INSR. Mutations of these loci have significant differences in phenotype and inheritance pattern. The most common genes associated with hyperinsulinism, involve the ABCC8 and KCNJ11 genes that encode the two subunits of the beta-cell ATP-dependent potassium channel. Recessive mutations of these genes cause a severe form of neonatal hypoglycemia that frequently requires near-total pancreatectomy. Diazoxide, a drug that acts as an agonist of the ATP-dependent potassium channel to suppress insulin secretion, is effective in defects associated with mutations of GLUD1 and HADHSC. Diazoxide is often ineffective in mutations of the ATP- dependent potassium channel and may not adequately control hypoglycemia in GCK or SLC16A1 mutations. |
Category | Inherited metabolic disorder |
Network | - |
Gene | (HHF1/ LIH) ABCC8 [HSA:6833] [KO:K05032] (HHF2) KCNJ11 [HSA:3767] [KO:K05004] (HHF3) GCK [HSA:2645] [KO:K12407] (HHF4) HADH [HSA:3033] [KO:K00022] (HHF5) INSR [HSA:3643] [KO:K04527] (HHF6) GLUD1 [HSA:2746] [KO:K00261] (HHF7) SLC16A1 [HSA:6566] [KO:K08179] (HHF8) SLC25A36 [HSA:55186] [KO:K15116] |
Pathogen | - |
Env factor | - |
Carcinogen | - |
Drug | Diazoxide [DR:D00294] |
Comment | Leucine-induced hypoglycemia (LIH) |
Other DBs | ICD-11: 5A45 ICD-10: E16.1 MeSH: D006946 OMIM: 256450 240800 601820 602485 609975 609968 606762 610021 620211 |
Reference | PMID:16356235 AUTHORS Lheureux PE, Zahir S, Penaloza A, Gris M TITLE Bench-to-bedside review: Antidotal treatment of sulfonylurea-induced hypoglycaemia with octreotide. JOURNAL Crit Care 9:543-9 (2005) DOI:10.1186/cc3807 PMID:21378225 AUTHORS Palladino AA, Stanley CA TITLE Nesidioblastosis no longer! It's all about genetics. JOURNAL J Clin Endocrinol Metab 96:617-9 (2011) DOI:10.1210/jc.2011-0164 PMID:16357843 (HHF1/2) AUTHORS Suchi M, MacMullen CM, Thornton PS, Adzick NS, Ganguly A, Ruchelli ED, Stanley CA TITLE Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism. JOURNAL Mod Pathol 19:122-9 (2006) DOI:10.1038/modpathol.3800497 PMID:15356046 (LIH) AUTHORS Magge SN, Shyng SL, MacMullen C, Steinkrauss L, Ganguly A, Katz LE, Stanley CA TITLE Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor. JOURNAL J Clin Endocrinol Metab 89:4450-6 (2004) DOI:10.1210/jc.2004-0441 PMID:9435328 (HHF3) AUTHORS Glaser B, Kesavan P, Heyman M, Davis E, Cuesta A, Buchs A, Stanley CA, Thornton PS, Permutt MA, Matschinsky FM, Herold KC TITLE Familial hyperinsulinism caused by an activating glucokinase mutation. JOURNAL N Engl J Med 338:226-30 (1998) DOI:10.1056/NEJM199801223380404 PMID:11489939 (HHF4) AUTHORS Clayton PT, Eaton S, Aynsley-Green A, Edginton M, Hussain K, Krywawych S, Datta V, Malingre HE, Berger R, van den Berg IE TITLE Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. JOURNAL J Clin Invest 108:457-65 (2001) DOI:10.1172/JCI11294 PMID:15161766 (HHF5) AUTHORS Hojlund K, Hansen T, Lajer M, Henriksen JE, Levin K, Lindholm J, Pedersen O, Beck-Nielsen H TITLE A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. JOURNAL Diabetes 53:1592-8 (2004) DOI:10.2337/diabetes.53.6.1592 PMID:9571255 (HHF6) AUTHORS Stanley CA, Lieu YK, Hsu BY, Burlina AB, Greenberg CR, Hopwood NJ, Perlman K, Rich BH, Zammarchi E, Poncz M TITLE Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. JOURNAL N Engl J Med 338:1352-7 (1998) DOI:10.1056/NEJM199805073381904 PMID:17701893 (HHF7) AUTHORS Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, Parton LE, Schuit F, Quintens R, Sipila I, Mayatepek E, Meissner T, Halestrap AP, Rutter GA, Kere J TITLE Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells. JOURNAL Am J Hum Genet 81:467-74 (2007) DOI:10.1086/520960 PMID:34576089 (HHF8) AUTHORS Jasper L, Scarcia P, Rust S, Reunert J, Palmieri F, Marquardt T TITLE Uridine Treatment of the First Known Case of SLC25A36 Deficiency. JOURNAL Int J Mol Sci 22:ijms22189929 (2021) DOI:10.3390/ijms22189929 |