KEGG   DISEASE: Familial hyperinsulinemic hypoglycemia (HHF)Help
Entry
H01267                      Disease                                

Name
Familial hyperinsulinemic hypoglycemia (HHF)
Description
Familial hyperinsulinemic hypoglycemia 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 disease
Brite
Human diseases [BR:br08402]
 Congenital disorders of metabolism
  Other congenital disorders of metabolism
   H01267  Familial hyperinsulinemic hypoglycemia (HHF)
Human diseases in ICD-10 classification [BR:br08403]
 4. Endocrine, nutritional and metabolic diseases (E00-E90)
  E15-E16  Other disorders of glucose regulation and pancreatic internal secretion
   E16  Other disorders of pancreatic internal secretion
    H01267  Familial hyperinsulinemic hypoglycemia (HHF)
BRITE hierarchy
Pathway
Glycolysis / Gluconeogenesis
Fatty acid degradation
D-Glutamine and D-glutamate metabolism
ABC transporters
Insulin signaling pathway
Type II diabetes mellitus
Gene
(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]
Drug
Diazoxide [DR:D00294]
Comment
Leucine-induced hypoglycemia (LIH)
Other DBs
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
PMID:16356235 (Drug)
  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
Reference
PMID:21378225 (Description)
  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
Reference
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

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