Hyperinsulinism Panel
GTR Test Accession: Help GTR000506422.8
CAP
INHERITED DISEASEENDOCRINOLOGYMETABOLIC DISEASE ... View more
Last updated in GTR: 2021-01-19
Last annual review date for the lab: 2023-07-18 LinkOut
At a Glance
Diagnosis; Monitoring; Mutation Confirmation; ...
Hyperinsulinemic hypoglycemia, familial, 1; Aldosterone-producing adenoma with seizures and neurological abnormalities; Congenital disorder of glycosylation; ...
ABCC8 (11p15.1), AKT2 (19q13.2), CACNA1D (3p21.1), CREBBP (16p13.3), EP300 (22q13.2), ...
Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...
The target population for this test is patients suspected of …
Mutations in several genes have been identified in familial forms …
Establish or confirm diagnosis
Ordering Information
Offered by: Help
Specimen Source: Help
Who can order: Help
  • Genetic Counselor
  • Health Care Provider
  • Licensed Physician
  • Nurse Practitioner
  • Physician Assistant
  • Registered Nurse
CPT codes: Help
**AMA CPT codes notice
Contact Policy: Help
Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.
How to Order: Help
All samples should be shipped via overnight delivery at room temperature.
No weekend or holiday deliveries.
Label each specimen with the patient’s name, date of birth and date sample collected.
Send specimens with complete requisition and consent form, otherwise, specimen processing may be delayed.
Order URL
Test service: Help
Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings
Test additional service: Help
Custom Prenatal Testing
Custom mutation-specific/Carrier testing
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
No
Pre-test genetic counseling required: Help
Decline to answer
Post-test genetic counseling required: Help
Decline to answer
Recommended fields not provided:
Conditions Help
Total conditions: 13
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 24
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 2
Method Category Help
Test method Help
Instrument *
Deletion/duplication analysis
Next-Generation (NGS)/Massively parallel sequencing (MPS)
Sequence analysis of the entire coding region
Next-Generation (NGS)/Massively parallel sequencing (MPS)
* Instrument: Not provided
Clinical Information
Test purpose: Help
Diagnosis; Monitoring; Mutation Confirmation; Pre-symptomatic; Risk Assessment; Screening
Clinical validity: Help
Mutations in several genes have been identified in familial forms of hyperinsulinism. Inactivating mutations in the genes encoding the two subunits of the ß-cell ATP-sensitive potassium channel (KATP channel), ABCC8 and KCNJ11, cause the most common and severe form of hyperinsulinism, although mutations in ABCC8 are more common (3-6). The … View more
View citations (20)
  • A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland. Otonkoski T, et al. Diabetes. 1999;48(2):408-15. doi:10.2337/diabetes.48.2.408. PMID: 10334322.
  • Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1. Huopio H, et al. J Clin Invest. 2000;106(7):897-906. doi:10.1172/JCI9804. PMID: 11018078.
  • Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. Clayton PT, et al. J Clin Invest. 2001;108(3):457-65. doi:10.1172/JCI11294. PMID: 11489939.
  • The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy. Christesen HB, et al. Diabetes. 2002;51(4):1240-6. doi:10.2337/diabetes.51.4.1240. PMID: 11916951.
  • Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. Molven A, et al. Diabetes. 2004;53(1):221-7. doi:10.2337/diabetes.53.1.221. PMID: 14693719.
  • A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. Højlund K, et al. Diabetes. 2004;53(6):1592-8. doi:10.2337/diabetes.53.6.1592. PMID: 15161766.
  • Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation. Cuesta-Muñoz AL, et al. Diabetes. 2004;53(8):2164-8. doi:10.2337/diabetes.53.8.2164. PMID: 15277402.
  • Congenital hyperinsulinism - a review of the disorder and a discussion of the anesthesia management. Hardy OT, et al. Paediatr Anaesth. 2007;17(7):616-21. doi:10.1111/j.1460-9592.2007.02192.x. PMID: 17564642.
  • Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. Pinney SE, et al. J Clin Invest. 2008;118(8):2877-86. doi:10.1172/JCI35414. PMID: 18596924.
  • Large islets, beta-cell proliferation, and a glucokinase mutation. Kassem S, et al. N Engl J Med. 2010;362(14):1348-50. doi:10.1056/NEJMc0909845. PMID: 20375417.
  • Bellanné-Chantelot C, Saint-Martin C, Ribeiro MJ, Vaury C, Verkarre V, Arnoux JB, Valayannopoulos V, Gobrecht S, Sempoux C, Rahier J, Fournet JC, Jaubert F, Aigrain Y, Nihoul-Fékété C, de Lonlay P. ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism. J Med Genet. 2010;47(11):752-9. doi:10.1136/jmg.2009.075416. Epub 2010 Aug 03. PMID: 20685672.
  • Genetics of congenital hyperinsulinemic hypoglycemia. Flanagan SE, et al. Semin Pediatr Surg. 2011;20(1):13-7. doi:10.1053/j.sempedsurg.2010.10.004. PMID: 21185998.
  • Macmullen CM, Zhou Q, Snider KE, Tewson PH, Becker SA, Aziz AR, Ganguly A, Shyng SL, Stanley CA. Diazoxide-unresponsive congenital hyperinsulinism in children with dominant mutations of the β-cell sulfonylurea receptor SUR1. Diabetes. 2011;60(6):1797-804. doi:10.2337/db10-1631. Epub 2011 May 02. PMID: 21536946.
  • ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia. Glaser B, et al. Genet Med. 2011;13(10):891-4. doi:10.1097/GIM.0b013e31821fea33. PMID: 21716120.
  • Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell. Oçal G, et al. J Pediatr Endocrinol Metab. 2011;24(11-12):1019-23. doi:10.1515/jpem.2011.347. PMID: 22308858.
  • Flanagan SE, Xie W, Caswell R, Damhuis A, Vianey-Saban C, Akcay T, Darendeliler F, Bas F, Guven A, Siklar Z, Ocal G, Berberoglu M, Murphy N, O'Sullivan M, Green A, Clayton PE, Banerjee I, Clayton PT, Hussain K, Weedon MN, Ellard S. Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation. Am J Hum Genet. 2013;92(1):131-6. doi:10.1016/j.ajhg.2012.11.017. Epub 2012 Dec 27. PMID: 23273570.
  • Hyperinsulinism in infants and children. Stanley CA, et al. Pediatr Clin North Am. 1997;44(2):363-74. doi:10.1016/s0031-3955(05)70481-8. PMID: 9130925.
  • Familial hyperinsulinism caused by an activating glucokinase mutation. Glaser B, et al. N Engl J Med. 1998;338(4):226-30. doi:10.1056/NEJM199801223380404. PMID: 9435328.
  • Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. Stanley CA, et al. N Engl J Med. 1998;338(19):1352-7. doi:10.1056/NEJM199805073381904. PMID: 9571255.
  • Bruining, G.J., Recent advances in hyperinsulinism and pathogenesis of diabetes mellitus. Current Opinion in Pediatrics 1990. 2: p. 758-76500.
Clinical utility: Help
Establish or confirm diagnosis
View citations (19)
  • A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland. Otonkoski T, et al. Diabetes. 1999;48(2):408-15. doi:10.2337/diabetes.48.2.408. PMID: 10334322.
  • Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1. Huopio H, et al. J Clin Invest. 2000;106(7):897-906. doi:10.1172/JCI9804. PMID: 11018078.
  • Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. Clayton PT, et al. J Clin Invest. 2001;108(3):457-65. doi:10.1172/JCI11294. PMID: 11489939.
  • The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy. Christesen HB, et al. Diabetes. 2002;51(4):1240-6. doi:10.2337/diabetes.51.4.1240. PMID: 11916951.
  • Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. Molven A, et al. Diabetes. 2004;53(1):221-7. doi:10.2337/diabetes.53.1.221. PMID: 14693719.
  • A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. Højlund K, et al. Diabetes. 2004;53(6):1592-8. doi:10.2337/diabetes.53.6.1592. PMID: 15161766.
  • Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation. Cuesta-Muñoz AL, et al. Diabetes. 2004;53(8):2164-8. doi:10.2337/diabetes.53.8.2164. PMID: 15277402.
  • Congenital hyperinsulinism - a review of the disorder and a discussion of the anesthesia management. Hardy OT, et al. Paediatr Anaesth. 2007;17(7):616-21. doi:10.1111/j.1460-9592.2007.02192.x. PMID: 17564642.
  • Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. Pinney SE, et al. J Clin Invest. 2008;118(8):2877-86. doi:10.1172/JCI35414. PMID: 18596924.
  • Large islets, beta-cell proliferation, and a glucokinase mutation. Kassem S, et al. N Engl J Med. 2010;362(14):1348-50. doi:10.1056/NEJMc0909845. PMID: 20375417.
  • Bellanné-Chantelot C, Saint-Martin C, Ribeiro MJ, Vaury C, Verkarre V, Arnoux JB, Valayannopoulos V, Gobrecht S, Sempoux C, Rahier J, Fournet JC, Jaubert F, Aigrain Y, Nihoul-Fékété C, de Lonlay P. ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism. J Med Genet. 2010;47(11):752-9. doi:10.1136/jmg.2009.075416. Epub 2010 Aug 03. PMID: 20685672.
  • Genetics of congenital hyperinsulinemic hypoglycemia. Flanagan SE, et al. Semin Pediatr Surg. 2011;20(1):13-7. doi:10.1053/j.sempedsurg.2010.10.004. PMID: 21185998.
  • Macmullen CM, Zhou Q, Snider KE, Tewson PH, Becker SA, Aziz AR, Ganguly A, Shyng SL, Stanley CA. Diazoxide-unresponsive congenital hyperinsulinism in children with dominant mutations of the β-cell sulfonylurea receptor SUR1. Diabetes. 2011;60(6):1797-804. doi:10.2337/db10-1631. Epub 2011 May 02. PMID: 21536946.
  • ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia. Glaser B, et al. Genet Med. 2011;13(10):891-4. doi:10.1097/GIM.0b013e31821fea33. PMID: 21716120.
  • Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell. Oçal G, et al. J Pediatr Endocrinol Metab. 2011;24(11-12):1019-23. doi:10.1515/jpem.2011.347. PMID: 22308858.
  • Flanagan SE, Xie W, Caswell R, Damhuis A, Vianey-Saban C, Akcay T, Darendeliler F, Bas F, Guven A, Siklar Z, Ocal G, Berberoglu M, Murphy N, O'Sullivan M, Green A, Clayton PE, Banerjee I, Clayton PT, Hussain K, Weedon MN, Ellard S. Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation. Am J Hum Genet. 2013;92(1):131-6. doi:10.1016/j.ajhg.2012.11.017. Epub 2012 Dec 27. PMID: 23273570.
  • Hyperinsulinism in infants and children. Stanley CA, et al. Pediatr Clin North Am. 1997;44(2):363-74. doi:10.1016/s0031-3955(05)70481-8. PMID: 9130925.
  • Familial hyperinsulinism caused by an activating glucokinase mutation. Glaser B, et al. N Engl J Med. 1998;338(4):226-30. doi:10.1056/NEJM199801223380404. PMID: 9435328.
  • Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. Stanley CA, et al. N Engl J Med. 1998;338(19):1352-7. doi:10.1056/NEJM199805073381904. PMID: 9571255.

Target population: Help
The target population for this test is patients suspected of having a diagnosis of Familial Hyperinsulinemic Hypoglycemia.
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
Variants are identified and evaluated using a custom collection of bioinformatic tools and comprehensively interpreted by our team of directors and genetic counselors.

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Yes.
Research:
Is research allowed on the sample after clinical testing is complete? Help
http://dnatesting.uchicago.edu/research-consent-form
Recommended fields not provided:
Technical Information
Availability: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
Analytical Sensitivity 99-100% Accuracy 100% Precision 100%
Assay limitations: Help
This assay covers the coding and immediate flanking regions of the included genes. Variants in the promoter region and in other non-coding regions will not be detected. Variants that occur within regions of high homology and/or repetitiveness may not be detected due to issues with alignment. The technical sensitivity of … View more
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP
VUS:
Software used to interpret novel variations Help
A custom collection of bioinformatics tools

Laboratory's policy on reporting novel variations Help
The laboratory reports novel variations.
Recommended fields not provided:
Regulatory Approval
FDA Review: Help
Category: FDA exercises enforcement discretion
Additional Information

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.