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IEMbase 0213: KCNJ11-related ATP-sensitive potassium channel pore-forming subunit deficiency

Scope

Field Value
IEMbase ID 213
Nosology 24.1.03.01
Gene KCNJ11
External IDs OMIM:601820; ORPHA:99886
Generated mapping UNMAPPED; best candidate Congenital_Isolated_Hyperinsulinism.yaml
Candidate DisMech targets Congenital_Isolated_Hyperinsulinism.yaml#KATP-HI Diffuse; KCNJ11/HHF2 gene section
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as KCNJ11-related ATP-sensitive potassium channel pore-forming subunit deficiency, with alternate labels persistent hyperinsulinemic hypoglycemia of infancy, hyperinsulinism of infancy 2, and HHF2. The record is autosomal recessive and treatability is marked yes.

The biochemical rows capture the congenital hyperinsulinism pattern: low plasma glucose, high insulin during hypoglycemia, suppressed free fatty acids, and suppressed ketones during hypoglycemia. Characteristic clinical rows include hyperinsulinism, hypoketotic hypoglycemia, and convulsions, with additional rows for macrosomia and possible later diabetes. Treatments listed by IEMbase include diazoxide, glucagon, glucose infusion, high-carbohydrate feeding, lanreotide or octreotide, and nifedipine.

DisMech phenotype coverage

Congenital_Isolated_Hyperinsulinism.yaml is the correct local target despite the generated UNMAPPED status. The entry explicitly covers ABCC8/KCNJ11 K-ATP-channel disease, diffuse and focal KATP hyperinsulinism subtypes, KCNJ11 variants as HHF2, unregulated beta-cell depolarization and insulin secretion, hyperinsulinemic hypoglycemia, suppressed ketogenesis, seizures, neurodevelopmental risk, macrosomia, maturity-onset diabetes in relevant subtypes, diazoxide, octreotide/lanreotide, glucose support, and surgical management for focal/diffuse disease.

Concordance and completeness

Judgement: generated false negative; resolve to Congenital_Isolated_Hyperinsulinism.yaml, preferably the KATP/HHF2 coverage.

IEMbase and DisMech agree on KCNJ11 as the ATP-sensitive potassium-channel pore subunit, hyperinsulinemic hypoglycemia, suppressed ketones and fatty acids, seizure risk, macrosomia, possible later diabetes, and several acute/chronic treatments. DisMech is richer for the causal beta-cell membrane-depolarization mechanism, K-ATP channel biology, focal versus diffuse histology, and surgery.

Curation actions

  • Correct the generated UNMAPPED status to local coverage in Congenital_Isolated_Hyperinsulinism.yaml.
  • Prefer subtype resolution to KATP hyperinsulinism/HHF2 rather than a generic congenital hyperinsulinism-only match.
  • No new standalone KCNJ11 disease file is needed unless the project later chooses to split every congenital hyperinsulinism gene subtype into a separate disorder.