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Hyperinsulinism due to INSR deficiency(HHF5)

MedGen UID:
355335
Concept ID:
C1864952
Disease or Syndrome
Synonyms: Hyperinsulinemic hypoglycemia familial 5; Hyperinsulinism due to glutamodehydrogenase deficiency
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): INSR (19p13.2)
 
Monarch Initiative: MONDO:0012381
OMIM®: 609968
Orphanet: ORPHA263458

Definition

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.

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. [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
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.
Fasting hyperinsulinemia
MedGen UID:
351259
Concept ID:
C1864954
Finding
An increased concentration of insulin in the blood in the fasting state, i.e., not as the response to food intake.
Elevated circulating insulin:C-peptide ratio
MedGen UID:
1815107
Concept ID:
C5706201
Finding
Increased ratio of insulin to C-peptide in the blood circulation.

Recent clinical studies

Etiology

Zhou HL, Grimmett ZW, Venetos NM, Stomberski CT, Qian Z, McLaughlin PJ, Bansal PK, Zhang R, Reynolds JD, Premont RT, Stamler JS
Cell 2023 Dec 21;186(26):5812-5825.e21. Epub 2023 Dec 5 doi: 10.1016/j.cell.2023.11.009. PMID: 38056462Free PMC Article
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
Meroni M, Longo M, Erconi V, Valenti L, Gatti S, Fracanzani AL, Dongiovanni P
Nutrients 2019 Oct 29;11(11) doi: 10.3390/nu11112597. PMID: 31671785Free PMC Article
Højlund K, Beck-Nielsen H, Flyvbjerg A, Frystyk J
Eur J Endocrinol 2012 Mar;166(3):511-9. Epub 2011 Dec 21 doi: 10.1530/EJE-11-0790. PMID: 22189999

Diagnosis

Henson J, Tziannou A, Rowlands AV, Edwardson CL, Hall AP, Davies MJ, Yates T
Diabetes Obes Metab 2024 Apr;26(4):1355-1365. Epub 2024 Jan 8 doi: 10.1111/dom.15437. PMID: 38186324
Skovsø S, Panzhinskiy E, Kolic J, Cen HH, Dionne DA, Dai XQ, Sharma RB, Elghazi L, Ellis CE, Faulkner K, Marcil SAM, Overby P, Noursadeghi N, Hutchinson D, Hu X, Li H, Modi H, Wildi JS, Botezelli JD, Noh HL, Suk S, Gablaski B, Bautista A, Kim R, Cras-Méneur C, Flibotte S, Sinha S, Luciani DS, Nislow C, Rideout EJ, Cytrynbaum EN, Kim JK, Bernal-Mizrachi E, Alonso LC, MacDonald PE, Johnson JD
Nat Commun 2022 Feb 8;13(1):735. doi: 10.1038/s41467-022-28039-8. PMID: 35136059Free PMC Article
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
Suliman SG, Stanik J, McCulloch LJ, Wilson N, Edghill EL, Misovicova N, Gasperikova D, Sandrikova V, Elliott KS, Barak L, Ellard S, Volpi EV, Klimes I, Gloyn AL
Diabetes 2009 Dec;58(12):2954-61. Epub 2009 Aug 31 doi: 10.2337/db09-0787. PMID: 19720790Free PMC Article
Kong WJ, Zhang H, Song DQ, Xue R, Zhao W, Wei J, Wang YM, Shan N, Zhou ZX, Yang P, You XF, Li ZR, Si SY, Zhao LX, Pan HN, Jiang JD
Metabolism 2009 Jan;58(1):109-19. doi: 10.1016/j.metabol.2008.08.013. PMID: 19059538

Therapy

Ha SE, Singh R, Jin B, Baek G, Jorgensen BG, Zogg H, Debnath S, Park HS, Cho H, Watkins CM, Cho S, Kim MS, Lee MY, Yu TY, Jeong JW, Ro S
Int J Mol Sci 2024 Sep 21;25(18) doi: 10.3390/ijms251810147. PMID: 39337631Free PMC Article
Cai W, Ramdas M, Zhu L, Chen X, Striker GE, Vlassara H
Proc Natl Acad Sci U S A 2012 Sep 25;109(39):15888-93. Epub 2012 Aug 20 doi: 10.1073/pnas.1205847109. PMID: 22908267Free PMC Article

Prognosis

Skovsø S, Panzhinskiy E, Kolic J, Cen HH, Dionne DA, Dai XQ, Sharma RB, Elghazi L, Ellis CE, Faulkner K, Marcil SAM, Overby P, Noursadeghi N, Hutchinson D, Hu X, Li H, Modi H, Wildi JS, Botezelli JD, Noh HL, Suk S, Gablaski B, Bautista A, Kim R, Cras-Méneur C, Flibotte S, Sinha S, Luciani DS, Nislow C, Rideout EJ, Cytrynbaum EN, Kim JK, Bernal-Mizrachi E, Alonso LC, MacDonald PE, Johnson JD
Nat Commun 2022 Feb 8;13(1):735. doi: 10.1038/s41467-022-28039-8. PMID: 35136059Free PMC Article

Clinical prediction guides

Henson J, Tziannou A, Rowlands AV, Edwardson CL, Hall AP, Davies MJ, Yates T
Diabetes Obes Metab 2024 Apr;26(4):1355-1365. Epub 2024 Jan 8 doi: 10.1111/dom.15437. PMID: 38186324
Skovsø S, Panzhinskiy E, Kolic J, Cen HH, Dionne DA, Dai XQ, Sharma RB, Elghazi L, Ellis CE, Faulkner K, Marcil SAM, Overby P, Noursadeghi N, Hutchinson D, Hu X, Li H, Modi H, Wildi JS, Botezelli JD, Noh HL, Suk S, Gablaski B, Bautista A, Kim R, Cras-Méneur C, Flibotte S, Sinha S, Luciani DS, Nislow C, Rideout EJ, Cytrynbaum EN, Kim JK, Bernal-Mizrachi E, Alonso LC, MacDonald PE, Johnson JD
Nat Commun 2022 Feb 8;13(1):735. doi: 10.1038/s41467-022-28039-8. PMID: 35136059Free PMC Article
Dongiovanni P, Meroni M, Baselli GA, Bassani GA, Rametta R, Pietrelli A, Maggioni M, Facciotti F, Trunzo V, Badiali S, Fargion S, Gatti S, Valenti L
Clin Sci (Lond) 2017 Jun 1;131(12):1301-1315. Epub 2017 Jun 7 doi: 10.1042/CS20170175. PMID: 28468951
Højlund K, Beck-Nielsen H, Flyvbjerg A, Frystyk J
Eur J Endocrinol 2012 Mar;166(3):511-9. Epub 2011 Dec 21 doi: 10.1530/EJE-11-0790. PMID: 22189999

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