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Hyperinsulinism due to glucokinase deficiency(HHF3)

MedGen UID:
355435
Concept ID:
C1865290
Disease or Syndrome
Synonyms: GCK-Related Hyperinsulinism; HHF3; Hyperinsulinemic hypoglycemia familial 3
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): GCK (7p13)
 
Monarch Initiative: MONDO:0011236
OMIM®: 602485
Orphanet: ORPHA79299

Definition

Congenital hyperinsulinism is a condition that causes individuals to have abnormally high levels of insulin. Insulin is a hormone that helps control levels of blood glucose, also called blood sugar. People with this condition have frequent episodes of low blood glucose (hypoglycemia). In infants and young children, these episodes are characterized by a lack of energy (lethargy), irritability, or difficulty feeding. Repeated episodes of low blood glucose increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma.

The severity of congenital hyperinsulinism varies widely among affected individuals, even among members of the same family. About 60 percent of infants with this condition experience a hypoglycemic episode within the first month of life. Other affected children develop hypoglycemia by early childhood. Unlike typical episodes of hypoglycemia, which occur most often after periods without food (fasting) or after exercising, episodes of hypoglycemia in people with congenital hyperinsulinism can also occur after eating. [from MedlinePlus Genetics]

Clinical features

From HPO
Hypoglycemic coma
MedGen UID:
5710
Concept ID:
C0020617
Disease or Syndrome
Coma induced by low blood sugar.
Hypoglycemic seizures
MedGen UID:
164079
Concept ID:
C0877056
Disease or Syndrome
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Hyperinsulinemic hypoglycemia
MedGen UID:
351247
Concept ID:
C1864903
Disease or Syndrome
An increased concentration of insulin combined with a decreased concentration of glucose in the blood.

Term Hierarchy

Follow this link to review classifications for Hyperinsulinism due to glucokinase deficiency in Orphanet.

Professional guidelines

PubMed

Maiorana A, Caviglia S, Greco B, Alfieri P, Cumbo F, Campana C, Bernabei SM, Cusmai R, Mosca A, Dionisi-Vici C
Orphanet J Rare Dis 2021 Oct 11;16(1):424. doi: 10.1186/s13023-021-02045-3. PMID: 34635134Free PMC Article

Recent clinical studies

Etiology

Douillard C, Jannin A, Vantyghem MC
Ann Endocrinol (Paris) 2020 Jun;81(2-3):110-117. Epub 2020 Apr 10 doi: 10.1016/j.ando.2020.04.003. PMID: 32409005
Gommers LM, Hoenderop JG, Bindels RJ, de Baaij JH
Diabetes 2016 Jan;65(1):3-13. doi: 10.2337/db15-1028. PMID: 26696633
Wang L, Huang J, Saha P, Kulkarni RN, Hu M, Kim Y, Park K, Chan L, Rajan AS, Lee I, Moore DD
Mol Endocrinol 2006 Nov;20(11):2671-81. Epub 2006 Jun 27 doi: 10.1210/me.2006-0224. PMID: 16803864
Kotani K, Peroni OD, Minokoshi Y, Boss O, Kahn BB
J Clin Invest 2004 Dec;114(11):1666-75. doi: 10.1172/JCI21341. PMID: 15578099Free PMC Article
Bogardus C
J Lab Clin Med 1995 May;125(5):556-8; discussion 559. PMID: 7738420

Diagnosis

de Sousa Melo SR, Dos Santos LR, da Cunha Soares T, Cardoso BEP, da Silva Dias TM, Morais JBS, de Paiva Sousa M, de Sousa TGV, da Silva NC, da Silva LD, Cruz KJC, do Nascimento Marreiro D
Biol Trace Elem Res 2022 Aug;200(8):3545-3553. Epub 2022 Jun 6 doi: 10.1007/s12011-021-02966-x. PMID: 35666386
Douillard C, Jannin A, Vantyghem MC
Ann Endocrinol (Paris) 2020 Jun;81(2-3):110-117. Epub 2020 Apr 10 doi: 10.1016/j.ando.2020.04.003. PMID: 32409005
Gommers LM, Hoenderop JG, Bindels RJ, de Baaij JH
Diabetes 2016 Jan;65(1):3-13. doi: 10.2337/db15-1028. PMID: 26696633
Douillard C, Mention K, Dobbelaere D, Wemeau JL, Saudubray JM, Vantyghem MC
Orphanet J Rare Dis 2012 May 15;7:26. doi: 10.1186/1750-1172-7-26. PMID: 22587661Free PMC Article
Giurgea I, Bellanné-Chantelot C, Ribeiro M, Hubert L, Sempoux C, Robert JJ, Blankenstein O, Hussain K, Brunelle F, Nihoul-Fékété C, Rahier J, Jaubert F, de Lonlay P
Horm Res 2006;66(6):289-96. Epub 2006 Sep 26 doi: 10.1159/000095938. PMID: 17003566

Therapy

Gommers LM, Hoenderop JG, Bindels RJ, de Baaij JH
Diabetes 2016 Jan;65(1):3-13. doi: 10.2337/db15-1028. PMID: 26696633
Whittington AC, Larion M, Bowler JM, Ramsey KM, Brüschweiler R, Miller BG
Proc Natl Acad Sci U S A 2015 Sep 15;112(37):11553-8. Epub 2015 Aug 17 doi: 10.1073/pnas.1506664112. PMID: 26283387Free PMC Article
Fajans SS, Bell GI, Bowden DW, Halter JB, Polonsky KS
Diabet Med 1996 Sep;13(9 Suppl 6):S90-5. PMID: 8894490

Prognosis

Maiorana A, Caviglia S, Greco B, Alfieri P, Cumbo F, Campana C, Bernabei SM, Cusmai R, Mosca A, Dionisi-Vici C
Orphanet J Rare Dis 2021 Oct 11;16(1):424. doi: 10.1186/s13023-021-02045-3. PMID: 34635134Free PMC Article
Cuesta-Muñoz AL, Huopio H, Otonkoski T, Gomez-Zumaquero JM, Näntö-Salonen K, Rahier J, López-Enriquez S, García-Gimeno MA, Sanz P, Soriguer FC, Laakso M
Diabetes 2004 Aug;53(8):2164-8. doi: 10.2337/diabetes.53.8.2164. PMID: 15277402
Dekelbab BH, Sperling MA
Diabetes Metab Res Rev 2004 May-Jun;20(3):189-95. doi: 10.1002/dmrr.448. PMID: 15133749
Molven A, Matre GE, Duran M, Wanders RJ, Rishaug U, Njølstad PR, Jellum E, Søvik O
Diabetes 2004 Jan;53(1):221-7. doi: 10.2337/diabetes.53.1.221. PMID: 14693719
Elbein SC, Sun J, Scroggin E, Teng K, Hasstedt SJ
Diabetes Care 2001 Mar;24(3):472-8. doi: 10.2337/diacare.24.3.472. PMID: 11289470

Clinical prediction guides

Giurgea I, Bellanné-Chantelot C, Ribeiro M, Hubert L, Sempoux C, Robert JJ, Blankenstein O, Hussain K, Brunelle F, Nihoul-Fékété C, Rahier J, Jaubert F, de Lonlay P
Horm Res 2006;66(6):289-96. Epub 2006 Sep 26 doi: 10.1159/000095938. PMID: 17003566
Cuesta-Muñoz AL, Huopio H, Otonkoski T, Gomez-Zumaquero JM, Näntö-Salonen K, Rahier J, López-Enriquez S, García-Gimeno MA, Sanz P, Soriguer FC, Laakso M
Diabetes 2004 Aug;53(8):2164-8. doi: 10.2337/diabetes.53.8.2164. PMID: 15277402
Molven A, Matre GE, Duran M, Wanders RJ, Rishaug U, Njølstad PR, Jellum E, Søvik O
Diabetes 2004 Jan;53(1):221-7. doi: 10.2337/diabetes.53.1.221. PMID: 14693719
Elbein SC, Sun J, Scroggin E, Teng K, Hasstedt SJ
Diabetes Care 2001 Mar;24(3):472-8. doi: 10.2337/diacare.24.3.472. PMID: 11289470
O'Rahilly S, Hattersley A, Vaag A, Gray H
Lancet 1994 Aug 27;344(8922):585-9. doi: 10.1016/s0140-6736(94)91969-0. PMID: 7914964

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