Congenital hyperinsulinism (CHI) is a heterogeneous genetic disorder of pancreatic β-cell characterized by persistent hypoglycemia (PHHI) in infants and children due to unregulated secretion of insulin. CHI is most commonly associated with inactivating mutations of the ATP– sensitive plasma membrane potassium (KATP) channel genes ABCC8 (encoding the sulfonylurea receptor 1, SUR1) and KCNJ11 ( inward rectifying potassium ion channel Kir6.2).
Why is it important to identify mutations in patients with CHI?
Genetic testing assists in understanding the nature of the molecular abnormality and in most cases the timely prediction of the type of hyperinsulinemia is likely to aid in avoiding hypoglycemia related brain damage.
Mutations in KCNJ11 or ABCC8 genes result in reduction or loss of KATP channel function that leads to constant depolarization of the cell membrane and persistent insulin secretion even at very low plasma glucose concentrations. Recessive mutations of these genes cause hyperinsulinism that is unresponsive to treatment with channel agonists like diazoxide, while dominant KATP mutations have been associated with diazoxide-responsive disease.
Genes screened for CHI
KCNJ11, ABCC8 and Insulin genes will be screened. In addition GLUD1 gene will also be screened for the patient with Hyperammonemia-hyperinsulinism.
Requirements for the genetic testing
Detailed clinical history along with blood/DNA samples from the patient, both parents and affected/unaffected siblings are required.
Consent Form – Mandatory to fill up and send along with the sample.
Download Congenital hyperinsulinism Requisition Form | Online CHI Registration
It is mandatory to fill this before any genetic testing has done.