IEMbase 0568: GCK-related glucokinase hyperinsulinism
Scope
| Field | Value |
|---|---|
| IEMbase ID | 568 |
| Nosology | 3.3.05.01 |
| Gene | GCK |
| External IDs | OMIM:602485; ORPHA:99885 |
| Generated mapping | UNMAPPED |
| Candidate DisMech targets | Congenital_Isolated_Hyperinsulinism.yaml#GCK-HI; Diabetes_Mellitus.yaml as monogenic diabetes context |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents GCK-related glucokinase superactivity, with alternate labels familial hyperinsulinemic hypoglycemia and HHF3. The record is autosomal dominant, idiopathic subtype, of unknown treatability, and has no treatment rows. The IEMbase alternate-name field also includes a MODY label, which should be source-reviewed because activating GCK disease is the hypoglycemic branch whereas other GCK variant classes sit in monogenic diabetes.
Biochemical rows include decreased serum free fatty acids, decreased ketones during hypoglycemia, very low to low plasma glucose, and increased plasma insulin. Clinical and characteristic rows include diabetes mellitus type 2, epilepsy, hypoglycemia, intellectual disability, hyperinsulinism, and hypoketotic hypoglycemia.
DisMech phenotype coverage
Congenital_Isolated_Hyperinsulinism.yaml contains an explicit GCK-HI subtype:
dominant activating glucokinase variants lower the beta-cell glucose threshold
for insulin secretion, producing hyperinsulinemic hypoglycemia of variable
severity. Diabetes_Mellitus.yaml also contains GCK under the monogenic
diabetes spectrum, but that broader diabetes context is not the best target for
the hyperinsulinemic GCK superactivity record.
Concordance and completeness
Judgement: generated false negative; resolve the hyperinsulinism aspect to
Congenital_Isolated_Hyperinsulinism.yaml#GCK-HI.
IEMbase and DisMech agree on GCK identity, dominant inheritance, hyperinsulinism, low glucose, suppressed ketones/free fatty acids, and inappropriate insulin secretion. DisMech is stronger for the glucose-sensor threshold mechanism. IEMbase is more explicit about epilepsy, intellectual disability, type 2 diabetes wording, and compartment-specific biochemical rows.
Curation actions
- Promote this record to
Congenital_Isolated_Hyperinsulinism.yaml#GCK-HI. - Keep
Diabetes_Mellitus.yamlonly as monogenic-diabetes context, not as the primary mapping for GCK superactivity. - Review the IEMbase MODY/type 2 diabetes wording against GCK activating versus inactivating variant mechanisms before importing aliases or phenotypes.