U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Hyperinsulinemic hypoglycemia

MedGen UID:
351247
Concept ID:
C1864903
Disease or Syndrome; Finding
Synonyms: Hyperinsulinemia hypoglycemia; Hyperinsulinemic hypoglycemia (disease)
 
HPO: HP:0000825
Monarch Initiative: MONDO:0005803
OMIM® Phenotypic series: PS256450
Orphanet: ORPHA443095

Definition

An increased concentration of insulin combined with a decreased concentration of glucose in the blood. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHyperinsulinemic hypoglycemia

Conditions with this feature

Leucine-induced hypoglycemia
MedGen UID:
82888
Concept ID:
C0271714
Disease or Syndrome
Islet cell adenomatosis
MedGen UID:
293643
Concept ID:
C1578917
Neoplastic Process
Insulinomatosis and diabetes mellitus syndrome is an autosomal dominant disorder in which affected individuals within a family present with either hyperinsulinemic hypoglycemia secondary to pancreatic neuroendocrine tumors, or a noninsulin-dependent form of diabetes mellitus. A few affected individuals show only impaired glucose tolerance. Some patients also exhibit congenital cataract and/or congenital glaucoma (Iacovazzo et al., 2018).
Hyperinsulinism-hyperammonemia syndrome
MedGen UID:
376153
Concept ID:
C1847555
Disease or Syndrome
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.\n\nThe 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.
Exercise-induced hyperinsulinism
MedGen UID:
351246
Concept ID:
C1864902
Disease or Syndrome
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.\n\nCongenital 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.
Hyperinsulinemic hypoglycemia, familial, 4
MedGen UID:
400646
Concept ID:
C1864948
Disease or Syndrome
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.\n\nThe 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.
Hyperinsulinism due to INSR deficiency
MedGen UID:
355335
Concept ID:
C1864952
Disease or Syndrome
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.\n\nCongenital 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.
MPI-congenital disorder of glycosylation
MedGen UID:
400692
Concept ID:
C1865145
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). For a discussion of the classification of CDGs, see CDG1A (212065). CDG Ib is clinically distinct from most other CDGs by the lack of significant central nervous system involvement. The predominant symptoms are chronic diarrhea with failure to thrive and protein-losing enteropathy with coagulopathy. Some patients develop hepatic fibrosis. CDG Ib is also different from other CDGs in that it can be treated effectively with oral mannose supplementation, but can be fatal if untreated (Marquardt and Denecke, 2003). Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy in order to allow early diagnosis and effective therapy (Vuillaumier-Barrot et al., 2002) Freeze and Aebi (1999) reviewed CDG Ib and CDG Ic (603147). Marques-da-Silva et al. (2017) systematically reviewed the literature concerning liver involvement in CDG.
Hyperinsulinism due to glucokinase deficiency
MedGen UID:
355435
Concept ID:
C1865290
Disease or Syndrome
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.\n\nThe 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.
Hyperinsulinemic hypoglycemia, familial, 1
MedGen UID:
419505
Concept ID:
C2931832
Disease or Syndrome
Familial hyperinsulinism, also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur (Thornton et al., 1998). Genetic Heterogeneity of Hyperinsulinemic Hypoglycemia HHF2 (601820) is caused by mutation in the KCNJ11 gene (600937) on chromosome 11p15. HHF3 (602485) is caused by mutation in the glucokinase gene (GCK; 138079) on chromosome 7p13. HHF4 (609975) is caused by mutation in the HADH gene (601609) on chromosome 4q25. HHF5 (609968) is caused by mutation in the insulin receptor gene (INSR; 147670) on chromosome 19p13. HHF6 (606762) is caused by mutation in the GLUD1 gene (138130) on chromosome 10q23. HHF7 (610021) is caused by mutation in the SLC16A1 (600682) on chromosome 1p13. There is evidence of further genetic heterogeneity of HHF.
Hyperinsulinemic hypoglycemia, familial, 2
MedGen UID:
419173
Concept ID:
C2931833
Disease or Syndrome
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.\n\nThe 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.
Microcephaly, short stature, and impaired glucose metabolism 1
MedGen UID:
863434
Concept ID:
C4014997
Disease or Syndrome
Microcephaly, short stature, and impaired glucose metabolism-1 (MSSGM1) is an autosomal recessive syndrome characterized by microcephaly associated with impaired intellectual development, short stature, and early-onset diabetes or abnormalities of glucose homeostasis (Igoillo-Esteve et al., 2013; Gillis et al., 2014). Genetic Heterogeneity of Microcephaly, Short Stature, and Impaired Glucose Metabolism MSSGM2 (616817) is caused by mutation in the PPP1R15B gene (613257) on chromosome 1q32. Also see Wolcott-Rallison syndrome (226980), which is characterized by multiple epiphyseal dysplasia, microcephaly, short stature, and early-onset diabetes mellitus and is caused by mutation in the EIF2AK3 gene (604032) on chromosome 2p11.
Liver disease, severe congenital
MedGen UID:
1823968
Concept ID:
C5774195
Disease or Syndrome
Severe congenital liver disease (SCOLIV) is an autosomal recessive disorder characterized by the onset of progressive hepatic dysfunction usually in the first years of life. Affected individuals show feeding difficulties with failure to thrive and features such as jaundice, hepatomegaly, and abdominal distension. Laboratory workup is consistent with hepatic insufficiency and may also show coagulation defects, anemia, or metabolic disturbances. Cirrhosis and hypernodularity are commonly observed on liver biopsy. Many patients die of liver failure in early childhood (Moreno Traspas et al., 2022).

Professional guidelines

PubMed

Kittah NE, Vella A
Eur J Endocrinol 2017 Jul;177(1):R37-R47. Epub 2017 Apr 5 doi: 10.1530/EJE-16-1062. PMID: 28381450
van Beek AP, Emous M, Laville M, Tack J
Obes Rev 2017 Jan;18(1):68-85. Epub 2016 Oct 17 doi: 10.1111/obr.12467. PMID: 27749997
Malik S, Mitchell JE, Steffen K, Engel S, Wiisanen R, Garcia L, Malik SA
Obes Res Clin Pract 2016 Jan-Feb;10(1):1-14. Epub 2015 Oct 27 doi: 10.1016/j.orcp.2015.07.003. PMID: 26522879Free PMC Article

Recent clinical studies

Etiology

Christ E, Iacovazzo D, Korbonits M, Perren A
Endocr Relat Cancer 2023 Jun 1;30(6) Epub 2023 May 16 doi: 10.1530/ERC-22-0327. PMID: 36952647
Sims K
Neoreviews 2021 Apr;22(4):e230-e240. doi: 10.1542/neo.22-4-e230. PMID: 33795398
Gϋemes M, Rahman SA, Kapoor RR, Flanagan S, Houghton JAL, Misra S, Oliver N, Dattani MT, Shah P
Rev Endocr Metab Disord 2020 Dec;21(4):577-597. doi: 10.1007/s11154-020-09548-7. PMID: 32185602Free PMC Article
Azim S, Kashyap SR
Endocrinol Metab Clin North Am 2016 Dec;45(4):905-921. Epub 2016 Oct 8 doi: 10.1016/j.ecl.2016.06.011. PMID: 27823611Free PMC Article
Güemes M, Hussain K
Pediatr Clin North Am 2015 Aug;62(4):1017-36. Epub 2015 May 13 doi: 10.1016/j.pcl.2015.04.010. PMID: 26210630

Diagnosis

Sims K
Neoreviews 2021 Apr;22(4):e230-e240. doi: 10.1542/neo.22-4-e230. PMID: 33795398
Gϋemes M, Rahman SA, Kapoor RR, Flanagan S, Houghton JAL, Misra S, Oliver N, Dattani MT, Shah P
Rev Endocr Metab Disord 2020 Dec;21(4):577-597. doi: 10.1007/s11154-020-09548-7. PMID: 32185602Free PMC Article
Kittah NE, Vella A
Eur J Endocrinol 2017 Jul;177(1):R37-R47. Epub 2017 Apr 5 doi: 10.1530/EJE-16-1062. PMID: 28381450
van Beek AP, Emous M, Laville M, Tack J
Obes Rev 2017 Jan;18(1):68-85. Epub 2016 Oct 17 doi: 10.1111/obr.12467. PMID: 27749997
Malik S, Mitchell JE, Steffen K, Engel S, Wiisanen R, Garcia L, Malik SA
Obes Res Clin Pract 2016 Jan-Feb;10(1):1-14. Epub 2015 Oct 27 doi: 10.1016/j.orcp.2015.07.003. PMID: 26522879Free PMC Article

Therapy

Zhang C, Zhang H, Huang W
Endocrine 2023 Apr;80(1):40-46. Epub 2022 Dec 2 doi: 10.1007/s12020-022-03268-5. PMID: 36459334Free PMC Article
van Beek AP, Emous M, Laville M, Tack J
Obes Rev 2017 Jan;18(1):68-85. Epub 2016 Oct 17 doi: 10.1111/obr.12467. PMID: 27749997
Malik S, Mitchell JE, Steffen K, Engel S, Wiisanen R, Garcia L, Malik SA
Obes Res Clin Pract 2016 Jan-Feb;10(1):1-14. Epub 2015 Oct 27 doi: 10.1016/j.orcp.2015.07.003. PMID: 26522879Free PMC Article
Güemes M, Hussain K
Pediatr Clin North Am 2015 Aug;62(4):1017-36. Epub 2015 May 13 doi: 10.1016/j.pcl.2015.04.010. PMID: 26210630
Straussman S, Levitsky LL
Curr Opin Endocrinol Diabetes Obes 2010 Feb;17(1):20-4. doi: 10.1097/MED.0b013e328334f061. PMID: 19952738

Prognosis

Zenker M, Mohnike K, Palm K
Front Endocrinol (Lausanne) 2023;14:1013874. Epub 2023 Mar 30 doi: 10.3389/fendo.2023.1013874. PMID: 37065762Free PMC Article
Zhang C, Zhang H, Huang W
Endocrine 2023 Apr;80(1):40-46. Epub 2022 Dec 2 doi: 10.1007/s12020-022-03268-5. PMID: 36459334Free PMC Article
Sims K
Neoreviews 2021 Apr;22(4):e230-e240. doi: 10.1542/neo.22-4-e230. PMID: 33795398
Dravecka I, Lazurova I
Neoplasma 2014;61(3):252-6. doi: 10.4149/neo_2014_047. PMID: 24645840
Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL
Hum Mutat 2009 Nov;30(11):1512-26. doi: 10.1002/humu.21110. PMID: 19790256

Clinical prediction guides

Gersing S, Cagiada M, Gebbia M, Gjesing AP, Coté AG, Seesankar G, Li R, Tabet D, Weile J, Stein A, Gloyn AL, Hansen T, Roth FP, Lindorff-Larsen K, Hartmann-Petersen R
Genome Biol 2023 Apr 26;24(1):97. doi: 10.1186/s13059-023-02935-8. PMID: 37101203Free PMC Article
Zenker M, Mohnike K, Palm K
Front Endocrinol (Lausanne) 2023;14:1013874. Epub 2023 Mar 30 doi: 10.3389/fendo.2023.1013874. PMID: 37065762Free PMC Article
Yoldas Celik M, Yazici H, Erdem F, Yuksel Yanbolu A, Aykut A, Durmaz A, Zeybek S, Canda E, Kalkan Ucar S, Coker M
J Pediatr Endocrinol Metab 2023 Jun 27;36(6):530-538. Epub 2023 Apr 13 doi: 10.1515/jpem-2022-0641. PMID: 37042760
Subbarayan A, Hussain K
Am J Med Genet A 2014 Feb;164A(2):467-71. Epub 2013 Dec 5 doi: 10.1002/ajmg.a.36256. PMID: 24311525
Matschinsky FM, Zelent B, Doliba NM, Kaestner KH, Vanderkooi JM, Grimsby J, Berthel SJ, Sarabu R
Handb Exp Pharmacol 2011;(203):357-401. doi: 10.1007/978-3-642-17214-4_15. PMID: 21484579

Recent systematic reviews

Brown N, Elston MS
J Clin Endocrinol Metab 2024 Mar 15;109(4):936-943. doi: 10.1210/clinem/dgad467. PMID: 37552775
Llewellyn DC, Logan Ellis H, Aylwin SJB, Oštarijaš E, Green S, Sheridan W, Chew NWS, le Roux CW, Miras AD, Patel AG, Vincent RP, Dimitriadis GK
Obesity (Silver Spring) 2023 Jan;31(1):20-30. Epub 2022 Dec 10 doi: 10.1002/oby.23600. PMID: 36502288Free PMC Article
Perge K, Nicolino M
Rev Endocr Metab Disord 2022 Oct;23(5):1063-1078. Epub 2022 Aug 23 doi: 10.1007/s11154-022-09749-2. PMID: 35996042
Chen X, Feng L, Yao H, Yang L, Qin Y
PLoS One 2021;16(2):e0246463. Epub 2021 Feb 11 doi: 10.1371/journal.pone.0246463. PMID: 33571197Free PMC Article
van Beek AP, Emous M, Laville M, Tack J
Obes Rev 2017 Jan;18(1):68-85. Epub 2016 Oct 17 doi: 10.1111/obr.12467. PMID: 27749997

Supplemental Content

Table of contents

    Clinical resources

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

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...