KEGG   DISEASE: Familial hyperinsulinemic hypoglycemia
H01267                      Disease                                

Familial hyperinsulinemic hypoglycemia
Secondary hyperammonemia [DS:H01400]
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.
Congenital disorder of metabolism
Human diseases [BR:br08402]
 Congenital disorders of metabolism
  Other congenital disorders of metabolism
   H01267  Familial hyperinsulinemic hypoglycemia
Human diseases in ICD-11 classification [BR:br08403]
 05 Endocrine, nutritional or metabolic diseases
  Endocrine diseases
   Other disorders of glucose regulation or pancreatic internal secretion
    5A45  Persistent hyperinsulinemic hypoglycaemia of infancy
     H01267  Familial hyperinsulinemic hypoglycemia
hsa04910  Insulin signaling pathway
hsa04911  Insulin secretion
hsa01200  Carbon metabolism
hsa04930  Type II diabetes mellitus
hsa02010  ABC transporters
(HHF1/ LIH) ABCC8 [HSA:6833] [KO:K05032]
(HHF2) KCNJ11 [HSA:3767] [KO:K05004]
(HHF3) GCK [HSA:2645] [KO:K12407]
(HHF4) HADHSC [HSA:3033] [KO:K00022]
(HHF5) INSR [HSA:3643] [KO:K04527]
(HHF6) GLUD1 [HSA:2746] [KO:K00261]
(HHF7) SLC16A1 [HSA:6566] [KO:K08179]
Diazoxide [DR:D00294]
Leucine-induced hypoglycemia (LIH)
Other DBs
ICD-11: 5A45
ICD-10: E16.1
MeSH: D006946
OMIM: 256450 601820 602485 609975 609968 606762 610021 240800
PMID:16357843 (HHF1/2)
Suchi M, MacMullen CM, Thornton PS, Adzick NS, Ganguly A, Ruchelli ED, Stanley CA
Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism.
Mod Pathol 19:122-9 (2006)
PMID:9435328 (HHF3)
Glaser B, Kesavan P, Heyman M, Davis E, Cuesta A, Buchs A, Stanley CA, Thornton PS, Permutt MA, Matschinsky FM, Herold KC
Familial hyperinsulinism caused by an activating glucokinase mutation.
N Engl J Med 338:226-30 (1998)
PMID:11489939 (HHF4)
Clayton PT, Eaton S, Aynsley-Green A, Edginton M, Hussain K, Krywawych S, Datta V, Malingre HE, Berger R, van den Berg IE
Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion.
J Clin Invest 108:457-65 (2001)
PMID:15161766 (HHF5)
Hojlund K, Hansen T, Lajer M, Henriksen JE, Levin K, Lindholm J, Pedersen O, Beck-Nielsen H
A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene.
Diabetes 53:1592-8 (2004)
PMID:9571255 (HHF6)
Stanley CA, Lieu YK, Hsu BY, Burlina AB, Greenberg CR, Hopwood NJ, Perlman K, Rich BH, Zammarchi E, Poncz M
Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene.
N Engl J Med 338:1352-7 (1998)
PMID:17701893 (HHF7)
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
Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells.
Am J Hum Genet 81:467-74 (2007)
PMID:16356235 (Drug)
Lheureux PE, Zahir S, Penaloza A, Gris M
Bench-to-bedside review: Antidotal treatment of sulfonylurea-induced hypoglycaemia with octreotide.
Crit Care 9:543-9 (2005)
PMID:21378225 (Description)
Palladino AA, Stanley CA
Nesidioblastosis no longer! It's all about genetics.
J Clin Endocrinol Metab 96:617-9 (2011)
PMID:15356046 (LIH)
Magge SN, Shyng SL, MacMullen C, Steinkrauss L, Ganguly A, Katz LE, Stanley CA
Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor.
J Clin Endocrinol Metab 89:4450-6 (2004)

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