BabyScreen+ newborn screening

Gene: GCK

Green List (high evidence)

Well reported gene-disease association. Inactivating loss of function variants are associated with MODY type II (MIM#125851) and diabetes mellitus, permanent neonatal 1 (MIM#606176). Activating gain of function variants have been associated with hyperinsulinemic hypoglycemia, and usually cluster in a discrete region of the protein termed the allosteric activator site.

Non-genetic confirmatory tests: glucose, insulin, free fatty acid levels.

Treatment: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

Particularly applicable to the AD hyperinsulinaemic hypoglycaemia

Created: 20 Oct 2022, 2:18 a.m. | Last Modified: 20 Oct 2022, 2:18 a.m.

Panel Version: 0.591

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Diabetes mellitus, noninsulin-dependent, late onset, AD (MIM#125853); Diabetes mellitus, permanent neonatal 1, AR (MIM#606176); Hyperinsulinemic hypoglycemia, familial, 3, AD (MIM#602485); MODY, type II, AD (MIM#125851)

Green List (high evidence)

can cause AR congenital hyperinsulinism or AD diabetes including MODY
may or may not be responsive to diazoxide
evidence of response to glibenclamide or sulphonylurea in some cases

Created: 18 Oct 2022, 3:29 a.m. | Last Modified: 18 Oct 2022, 3:29 a.m.

Panel Version: 0.583

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
hypoglycaemia

Publications

• PMID: 19790256