U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Hepatocyte Nuclear Factor 1-Alpha Hyperinsulinism

MedGen UID:
1375363
•Concept ID:
C4330255
•
Disease or Syndrome

Definition

Hyperinsulinism due to mutation(s) in the gene HNF1A, encoding the transcription factor hepatocyte nuclear factor 1-alpha. This condition may progress to diabetes later in life. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHepatocyte Nuclear Factor 1-Alpha Hyperinsulinism

Professional guidelines

PubMed

Diagnosis and management of hyperinsulinaemic hypoglycaemia.
Galcheva S, Al-Khawaga S, Hussain K
Best Pract Res Clin Endocrinol Metab 2018 Aug;32(4):551-573. Epub 2018 Jun 6 doi: 10.1016/j.beem.2018.05.014. PMID: 30086874

Recent clinical studies

Etiology

Clinical heterogeneity of hyperinsulinism due to HNF1A and HNF4A mutations.
Tung JY, Boodhansingh K, Stanley CA, De León DD
Pediatr Diabetes 2018 Aug;19(5):910-916. Epub 2018 Mar 1 doi: 10.1111/pedi.12655. PMID: 29493090Free PMC Article
Association study of HNF1A polymorphisms with metabolic syndrome in the Moroccan population.
Morjane I, Kefi R, Charoute H, Lakbakbi El Yaagoubi F, Hechmi M, Saile R, Abdelhak S, Barakat A
Diabetes Metab Syndr 2017 Dec;11 Suppl 2:S853-S857. Epub 2017 Jul 3 doi: 10.1016/j.dsx.2017.07.005. PMID: 28712822
Clinical and Genetic Features of Patients With Type 2 Diabetes and Renal Glycosuria.
Gong S, Guo J, Han X, Li M, Zhou L, Cai X, Zhu Y, Luo Y, Zhang S, Zhou X, Ma Y, Ji L
J Clin Endocrinol Metab 2017 May 1;102(5):1548-1556. doi: 10.1210/jc.2016-2332. PMID: 28324025
The A98V single nucleotide polymorphism (SNP) in hepatic nuclear factor 1 alpha (HNF-1alpha) is associated with insulin sensitivity and beta-cell function.
Bergmann A, Li J, Selisko T, Reimann M, Fischer S, Grässler J, Schulze J, Bornstein SR, Schwarz PE
Exp Clin Endocrinol Diabetes 2008 Sep;116 Suppl 1:S50-5. Epub 2008 Sep 5 doi: 10.1055/s-2008-1081492. PMID: 18777455
Contrasting insulin sensitivity of endogenous glucose production rate in subjects with hepatocyte nuclear factor-1beta and -1alpha mutations.
Brackenridge A, Pearson ER, Shojaee-Moradie F, Hattersley AT, Russell-Jones D, Umpleby AM
Diabetes 2006 Feb;55(2):405-11. doi: 10.2337/diabetes.55.02.06.db05-1019. PMID: 16443774

Diagnosis

Diagnosis and management of hyperinsulinaemic hypoglycaemia.
Galcheva S, Al-Khawaga S, Hussain K
Best Pract Res Clin Endocrinol Metab 2018 Aug;32(4):551-573. Epub 2018 Jun 6 doi: 10.1016/j.beem.2018.05.014. PMID: 30086874
Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia.
Colclough K, Bellanne-Chantelot C, Saint-Martin C, Flanagan SE, Ellard S
Hum Mutat 2013 May;34(5):669-85. Epub 2013 Apr 2 doi: 10.1002/humu.22279. PMID: 23348805
DAX-1 acts as a novel corepressor of orphan nuclear receptor HNF4alpha and negatively regulates gluconeogenic enzyme gene expression.
Nedumaran B, Hong S, Xie YB, Kim YH, Seo WY, Lee MW, Lee CH, Koo SH, Choi HS
J Biol Chem 2009 Oct 2;284(40):27511-23. Epub 2009 Aug 3 doi: 10.1074/jbc.M109.034660. PMID: 19651776Free PMC Article
Contrasting insulin sensitivity of endogenous glucose production rate in subjects with hepatocyte nuclear factor-1beta and -1alpha mutations.
Brackenridge A, Pearson ER, Shojaee-Moradie F, Hattersley AT, Russell-Jones D, Umpleby AM
Diabetes 2006 Feb;55(2):405-11. doi: 10.2337/diabetes.55.02.06.db05-1019. PMID: 16443774
beta-cell genes and diabetes: quantitative and qualitative differences in the pathophysiology of hepatic nuclear factor-1alpha and glucokinase mutations.
Pearson ER, Velho G, Clark P, Stride A, Shepherd M, Frayling TM, Bulman MP, Ellard S, Froguel P, Hattersley AT
Diabetes 2001 Feb;50 Suppl 1:S101-7. doi: 10.2337/diabetes.50.2007.s101. PMID: 11272165

Therapy

Clinical and genetic heterogeneity of HNF4A/HNF1A mutations in a multicentre paediatric cohort with hyperinsulinaemic hypoglycaemia.
McGlacken-Byrne SM, Mohammad JK, Conlon N, Gubaeva D, Siersbæk J, Schou AJ, Demirbilek H, Dastamani A, Houghton JAL, Brusgaard K, Melikyan M, Christesen H, Flanagan SE, Murphy NP, Shah P
Eur J Endocrinol 2022 Feb 22;186(4):417-427. doi: 10.1530/EJE-21-0897. PMID: 35089870
Diagnosis and management of hyperinsulinaemic hypoglycaemia.
Galcheva S, Al-Khawaga S, Hussain K
Best Pract Res Clin Endocrinol Metab 2018 Aug;32(4):551-573. Epub 2018 Jun 6 doi: 10.1016/j.beem.2018.05.014. PMID: 30086874
Clinical heterogeneity of hyperinsulinism due to HNF1A and HNF4A mutations.
Tung JY, Boodhansingh K, Stanley CA, De León DD
Pediatr Diabetes 2018 Aug;19(5):910-916. Epub 2018 Mar 1 doi: 10.1111/pedi.12655. PMID: 29493090Free PMC Article
Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene.
Selva DM, Hogeveen KN, Innis SM, Hammond GL
J Clin Invest 2007 Dec;117(12):3979-87. doi: 10.1172/JCI32249. PMID: 17992261Free PMC Article
Contrasting insulin sensitivity of endogenous glucose production rate in subjects with hepatocyte nuclear factor-1beta and -1alpha mutations.
Brackenridge A, Pearson ER, Shojaee-Moradie F, Hattersley AT, Russell-Jones D, Umpleby AM
Diabetes 2006 Feb;55(2):405-11. doi: 10.2337/diabetes.55.02.06.db05-1019. PMID: 16443774

Prognosis

Congenital hyperinsulinism due to mutations in HNF1A.
Yau D, Colclough K, Natarajan A, Parikh R, Canham N, Didi M, Senniappan S, Banerjee I
Eur J Med Genet 2020 Jun;63(6):103928. Epub 2020 Apr 20 doi: 10.1016/j.ejmg.2020.103928. PMID: 32325224
Clinical heterogeneity of hyperinsulinism due to HNF1A and HNF4A mutations.
Tung JY, Boodhansingh K, Stanley CA, De León DD
Pediatr Diabetes 2018 Aug;19(5):910-916. Epub 2018 Mar 1 doi: 10.1111/pedi.12655. PMID: 29493090Free PMC Article
Williams-beuren syndrome is a genetic disorder associated with impaired glucose tolerance and diabetes in childhood and adolescence: new insights from a longitudinal study.
Stagi S, Lapi E, Cecchi C, Chiarelli F, D'Avanzo MG, Seminara S, de Martino M
Horm Res Paediatr 2014;82(1):38-43. Epub 2014 Jun 11 doi: 10.1159/000360476. PMID: 24925026
Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene.
Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, Ellard S, Ferrer J, Hattersley AT
PLoS Med 2007 Apr;4(4):e118. doi: 10.1371/journal.pmed.0040118. PMID: 17407387Free PMC Article
Role of common sequence variants in insulin secretion in familial type 2 diabetic kindreds: the sulfonylurea receptor, glucokinase, and hepatocyte nuclear factor 1alpha genes.
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

Congenital hyperinsulinism due to mutations in HNF1A.
Yau D, Colclough K, Natarajan A, Parikh R, Canham N, Didi M, Senniappan S, Banerjee I
Eur J Med Genet 2020 Jun;63(6):103928. Epub 2020 Apr 20 doi: 10.1016/j.ejmg.2020.103928. PMID: 32325224
Clinical heterogeneity of hyperinsulinism due to HNF1A and HNF4A mutations.
Tung JY, Boodhansingh K, Stanley CA, De León DD
Pediatr Diabetes 2018 Aug;19(5):910-916. Epub 2018 Mar 1 doi: 10.1111/pedi.12655. PMID: 29493090Free PMC Article
Transcription factor 1 and beta-cell function in glucose-tolerant subjects.
Chiu KC, Chuang LM, Chu A, Wang M
Diabet Med 2003 Mar;20(3):225-30. doi: 10.1046/j.1464-5491.2003.00905.x. PMID: 12675668
Role of common sequence variants in insulin secretion in familial type 2 diabetic kindreds: the sulfonylurea receptor, glucokinase, and hepatocyte nuclear factor 1alpha genes.
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
Genetic and clinical characterisation of maturity-onset diabetes of the young in Spanish families.
Costa A, Bescós M, Velho G, Chêvre J, Vidal J, Sesmilo G, Bellanné-Chantelot C, Froguel P, Casamitjana R, Rivera-Fillat F, Gomis R, Conget I
Eur J Endocrinol 2000 Apr;142(4):380-6. doi: 10.1530/eje.0.1420380. PMID: 10754480

Supplemental Content

Table of contents

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Related information

    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...