Details of Disease

General Information of Disease (ID: DIS3KP5D)

• Disease Name: Hyperinsulinemic hypoglycemia
• Synonyms: nesidioblastosis; hyperinsulinemia hypoglycemia; persistent hyperinsulinemia hypoglycemia of infancy; islet cell hyperplasia; hyperinsulinemic hypoglycemia (disease)
• Definition: An inherited autosomal recessive syndrome characterized by the disorganized formation of new islets in the pancreas and congenital hyperinsulinism. It is due to focal hyperplasia of pancreatic islet cells budding off from the ductal structures and forming new islets of langerhans. Mutations in the islet cells involve the potassium channel gene kcnj11 or the atp-binding cassette transporter gene abcc8, both on chromosome 11.
• Disease Hierarchy:
  DISRGY2N: Endocrine disease
  DISV24X3: Carbohydrate metabolism disorder
  DIS3KP5D: Hyperinsulinemic hypoglycemia
• Disease Identifiers:
  MONDO ID: MONDO_0005803
  UMLS CUI: C1864903
  MedGen ID: 351247
  HPO ID: HP:0000825
  Orphanet ID: 443095

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
UCP2	TTSC2YM	moderate	Biomarker	[1]
GCG	TT6Y4PN	Strong	Biomarker	[2]
GLP1R	TTVIMDE	Strong	Biomarker	[3]
HNF1A	TT01M3K	Strong	Biomarker	[4]
INSR	TTCBFJO	Strong	Genetic Variation	[5]
NSD1	TTTSJ3H	Strong	Biomarker	[6]
SLC16A1	TTN1J82	Strong	Biomarker	[7]
CACNA1D	TT7RGTM	Definitive	Genetic Variation	[8]
GCK	TTDLNGZ	Definitive	Genetic Variation	[9]
KCNJ11	TT329V4	Definitive	Genetic Variation	[10]

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PMM2	DEBRX3L	Limited	Genetic Variation	[11]
PGM1	DEA3VM1	Definitive	Biomarker	[12]
UGDH	DE48Q2Z	Definitive	Biomarker	[13]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
FOXA2	OTJOCVOY	Limited	Biomarker	[14]
MEN1	OTN6U6V0	Strong	Genetic Variation	[15]
RIT2	OTSNYG0D	Strong	Biomarker	[16]
CRYL1	OT0SJSJM	Definitive	Biomarker	[13]
GPR83	OT7A2FE8	Definitive	Altered Expression	[17]
H6PD	OTO7TNDD	Definitive	Biomarker	[13]

References

• [1] Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion. PLoS One. 2008;3(12):e3850. doi: 10.1371/journal.pone.0003850. Epub 2008 Dec 9.
• [2] Glucagon-like peptide 1 (GLP-1) drives postprandial hyperinsulinemic hypoglycemia in pregnant women with a history of Roux-en-Y gastric bypass operation.Metabolism. 2019 Feb;91:10-17. doi: 10.1016/j.metabol.2018.10.006. Epub 2018 Nov 15.
• [3] Hyperinsulinaemic hypoglycaemia-an overview of a complex clinical condition.Eur J Pediatr. 2019 Aug;178(8):1151-1160. doi: 10.1007/s00431-019-03414-8. Epub 2019 Jun 26.
• [4] Congenital Hyperinsulinism and Evolution to Sulfonylurearesponsive Diabetes Later in Life due to a Novel Homozygous p.L171F ABCC8 Mutation.J Clin Res Pediatr Endocrinol. 2019 Feb 20;11(1):82-87. doi: 10.4274/jcrpe.galenos.2018.2018.0077. Epub 2018 Mar 29.
• [5] Hyperinsulinemic hypoglycemia syndrome associated with mutations in the human insulin receptor gene: report of two cases.Endocr J. 2015;62(4):353-62. doi: 10.1507/endocrj.EJ14-0547. Epub 2015 Mar 5.
• [6] Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations.Am J Med Genet A. 2019 Apr;179(4):542-551. doi: 10.1002/ajmg.a.61062. Epub 2019 Feb 4.
• [7] Ion Transporters, Channelopathies, and Glucose Disorders.Int J Mol Sci. 2019 May 27;20(10):2590. doi: 10.3390/ijms20102590.
• [8] A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia.Pediatr Diabetes. 2017 Jun;18(4):320-323. doi: 10.1111/pedi.12512. Epub 2017 Mar 20.
• [9] Clinical and enzymatic phenotypes in congenital hyperinsulinemic hypoglycemia due to glucokinase-activating mutations: A report of two cases and a brief overview of the literature.J Diabetes Investig. 2019 Nov;10(6):1454-1462. doi: 10.1111/jdi.13072. Epub 2019 Jun 12.
• [10] Coexistence of Mosaic Uniparental Isodisomy and a KCNJ11 Mutation Presenting as Diffuse Congenital Hyperinsulinism and Hemihypertrophy.Horm Res Paediatr. 2016;85(6):421-5. doi: 10.1159/000446153. Epub 2016 May 14.
• [11] Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2.J Am Soc Nephrol. 2017 Aug;28(8):2529-2539. doi: 10.1681/ASN.2016121312. Epub 2017 Apr 3.
• [12] Congenital Hyperinsulinism: Diagnosis and Treatment Update.J Clin Res Pediatr Endocrinol. 2017 Dec 30;9(Suppl 2):69-87. doi: 10.4274/jcrpe.2017.S007. Epub 2017 Dec 27.
• [13] Leucine-sensitive hyperinsulinaemic hypoglycaemia in patients with loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase.Orphanet J Rare Dis. 2012 May 14;7:25. doi: 10.1186/1750-1172-7-25.
• [14] Conditional Tissue-Specific Foxa2 Ablation in Mouse Pancreas Causes Hyperinsulinemic Hypoglycemia: RETRACTED.Am J Ther. 2017 Mar/Apr;24(2):e1442-e1448. doi: 10.1097/MJT.0000000000000399.
• [15] Multiple Endocrine Neoplasia Type 1 Presenting as Hypoglycemia due to Insulinoma.J Korean Med Sci. 2016 Jun;31(6):1003-6. doi: 10.3346/jkms.2016.31.6.1003. Epub 2016 Apr 11.
• [16] O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) uptake in insulinoma: first results from a xenograft mouse model and from human.Nucl Med Biol. 2017 Oct;53:21-28. doi: 10.1016/j.nucmedbio.2017.07.005. Epub 2017 Jul 12.
• [17] Transient neonatal hyperinsulinaemic hypoglycaemia: perinatal predictors of length and cost of stay.Eur J Pediatr. 2018 Dec;177(12):1823-1829. doi: 10.1007/s00431-018-3242-7. Epub 2018 Sep 19.