Details of Disease

General Information of Disease (ID: DISHQKQE)

• Disease Name: Familial hyperinsulinism
• Synonyms: hyperinsulinemic hypoglycemia; neonatal hyperinsulinism; hereditary hyperinsulinism (disease); FHI; HHI; hyperinsulinemia of infancy; nesidioblastosis; familial hyperinsulinemic hypoglycemia; congenital hyperinsulinism
• Definition: An instance of hyperinsulinism (disease) that is caused by an inherited modification of the individual's genome.
• Disease Hierarchy:
  DISIDWT6: Hyperinsulinemia
  DIS3KP5D: Hyperinsulinemic hypoglycemia
  DISHQKQE: Familial hyperinsulinism
• Disease Identifiers:
  MONDO ID: MONDO_0017182
  MESH ID: D044903
  UMLS CUI: C3888018
  MedGen ID: 854723
  Orphanet ID: 276525
  SNOMED CT ID: 360339005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
KCNJ11	TT329V4	Limited	Genetic Variation	[1]
NSD1	TTTSJ3H	Limited	Biomarker	[2]
PDX1	TT8SGZK	Disputed	Altered Expression	[3]
GCG	TT6Y4PN	Strong	Biomarker	[4]
HAO1	TTS58YO	Strong	Biomarker	[5]
HNF1A	TT01M3K	Strong	Genetic Variation	[6]
INSR	TTCBFJO	Strong	Biomarker	[7]
MAP4K3	TTI0AHJ	Strong	Genetic Variation	[8]
SLC16A1	TTN1J82	Strong	Biomarker	[9]
SST	TTWF7UG	Strong	Biomarker	[1]
UCP2	TTSC2YM	Strong	Genetic Variation	[10]
TRPC4	TTX0H5W	Definitive	Biomarker	[11]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCC8	DTI58LU	Definitive	Autosomal recessive	[12]

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PGM1	DEA3VM1	Limited	Genetic Variation	[13]
HSD17B10	DEGSPC9	Definitive	Genetic Variation	[14]
PMM2	DEBRX3L	Definitive	Genetic Variation	[15]

This Disease Is Related to 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
EHHADH	OTBAAHL5	Strong	Genetic Variation	[16]
FOXA2	OTJOCVOY	Strong	Biomarker	[17]
HAO2	OTDWSQ0L	Strong	Biomarker	[5]
MED25	OTDBY87B	Strong	Biomarker	[18]
MEN1	OTN6U6V0	Strong	Genetic Variation	[19]
PDHX	OTG7O271	Strong	Altered Expression	[3]
RIT2	OTSNYG0D	Strong	Biomarker	[20]
SAR1A	OTSSRVGV	Strong	Biomarker	[21]
SKIL	OTNBXH32	Strong	Genetic Variation	[22]
ABCC8	OTCWQ54I	Definitive	Autosomal recessive	[12]

References

• [1] The Use of a Long-Acting Somatostatin Analogue (Lanreotide) in Three Children with Focal Forms of Congenital Hyperinsulinaemic Hypoglycaemia.Horm Res Paediatr. 2019;91(1):56-61. doi: 10.1159/000491101. Epub 2018 Aug 16.
• [2] 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.
• [3] Growth restriction and exendin 4 promote endocrine expression in cultured islet cells derived from patients with persistent hyperinsulinemic hypoglycemia of infancy (PHHI).Endocr Res. 2005;31(2):99-109. doi: 10.1080/07435800500229235.
• [4] 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.
• [5] Glycolate oxidase deficiency in a patient with congenital hyperinsulinism and unexplained hyperoxaluria.Pediatr Nephrol. 2017 Nov;32(11):2159-2163. doi: 10.1007/s00467-017-3741-1. Epub 2017 Jul 27.
• [6] The Diagnosis and Management of Hyperinsulinaemic Hypoglycaemia.J Clin Res Pediatr Endocrinol. 2015 Jun;7(2):86-97. doi: 10.4274/jcrpe.1891.
• [7] A unique allosteric insulin receptor monoclonal antibody that prevents hypoglycemia in the SUR-1(-/-) mouse model of KATP hyperinsulinism.MAbs. 2018 Jul;10(5):796-802. doi: 10.1080/19420862.2018.1457599. Epub 2018 Jun 1.
• [8] Activating mutations in the human glucokinase gene revealed by genetic selection.Biochemistry. 2009 Feb 10;48(5):814-6. doi: 10.1021/bi802142q.
• [9] Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism.Eur J Endocrinol. 2013 Mar 15;168(4):557-64. doi: 10.1530/EJE-12-0673. Print 2013 Apr.
• [10] Novel Hypoglycemia Phenotype in Congenital Hyperinsulinism Due to Dominant Mutations of Uncoupling Protein 2.J Clin Endocrinol Metab. 2017 Mar 1;102(3):942-949. doi: 10.1210/jc.2016-3164.
• [11] Regulation of K(ATP) Channel Trafficking in Pancreatic -Cells by Protein Histidine Phosphorylation.Diabetes. 2018 May;67(5):849-860. doi: 10.2337/db17-1433. Epub 2018 Feb 12.
• [12] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [13] Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1.Indian J Pediatr. 2019 Nov;86(11):1051-1053. doi: 10.1007/s12098-019-02980-x. Epub 2019 May 22.
• [14] Dominantly inherited hyperinsulinaemic hypoglycaemia.J Inherit Metab Dis. 2005;28(3):267-76. doi: 10.1007/s10545-005-7057-0.
• [15] 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.
• [16] Rare forms of congenital hyperinsulinism.Semin Pediatr Surg. 2011 Feb;20(1):38-44. doi: 10.1053/j.sempedsurg.2010.10.006.
• [17] Congenital Hyperinsulinism and Hypopituitarism Attributable to a Mutation in FOXA2.J Clin Endocrinol Metab. 2018 Mar 1;103(3):1042-1047. doi: 10.1210/jc.2017-02157.
• [18] 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation.Eur J Nucl Med Mol Imaging. 2018 Feb;45(2):250-261. doi: 10.1007/s00259-017-3867-1. Epub 2017 Nov 8.
• [19] 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.
• [20] 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.
• [21] Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation causing congenital hyperinsulinism.Hum Mol Genet. 2009 Jul 1;18(13):2400-13. doi: 10.1093/hmg/ddp179. Epub 2009 Apr 8.
• [22] Intraductal papillary mucinous neoplasm in a neonate with congenital hyperinsulinism and a de novo germline SKIL gene mutation.Pancreatology. 2015 Mar-Apr;15(2):194-6. doi: 10.1016/j.pan.2014.10.009. Epub 2014 Oct 27.