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IEMbase 0566: ABCC8-related congenital hyperinsulinism

Scope

Field Value
IEMbase ID 566
Nosology 24.1.01.01
Gene ABCC8
External IDs OMIM:256450; ORPHA:99886
Generated mapping UNMAPPED
Candidate DisMech targets Congenital_Isolated_Hyperinsulinism.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents ABCC8-related ATP-sensitive potassium channel regulatory subunit deficiency, with alternate label persistent hyperinsulinemic hypoglycemia of infancy and abbreviation HHF1. The record lists autosomal dominant and autosomal recessive inheritance, diffuse and focal form subtype, treatability yes, and no treatment rows.

Biochemical rows include very low serum free fatty acids during hypoglycemia, very low ketones during hypoglycemia, low plasma glucose, and high insulin during hypoglycemia. Clinical rows include optional diabetes or diabetes mellitus, macrosomia, convulsions, hyperinsulinism, and hypoketotic hypoglycemia.

DisMech phenotype coverage

Congenital_Isolated_Hyperinsulinism.yaml is the correct local target. It models congenital isolated hyperinsulinism as dysregulated glucose-independent insulin secretion from pancreatic beta cells. The entry explicitly includes diffuse and focal KATP hyperinsulinism caused by ABCC8 or KCNJ11, ABCC8/SUR1 as the K-ATP channel regulatory subunit, dominant and recessive forms, unregulated beta-cell depolarization, inappropriate insulin secretion, hyperinsulinemic hypoglycemia, suppressed ketogenesis, seizures, macrosomia, and genotype-sensitive treatment such as diazoxide or surgery.

Concordance and completeness

Judgement: generated false negative; resolve to Congenital_Isolated_Hyperinsulinism.yaml#KATP-HI/ABCC8.

IEMbase and DisMech agree on ABCC8 identity, K-ATP channel biology, dominant and recessive inheritance, diffuse and focal forms, hyperinsulinism, low glucose, hypoketotic hypoglycemia, suppressed free fatty acids and ketones, macrosomia, and convulsions/seizures. DisMech is stronger for the beta-cell depolarization and treatment mechanism.

IEMbase adds a useful HHF1-specific source row set and should be reconciled with the broader local ABCC8/KCNJ11 KATP-HI subtype.

Curation actions

  • Promote the IEMbase match to Congenital_Isolated_Hyperinsulinism.yaml, specifically the ABCC8/HHF1 KATP-HI branch.
  • Verify that PHHI and HHF1 aliases are visible enough for future matcher runs.
  • Review IEMbase diabetes, free-fatty-acid, ketone, glucose, insulin, macrosomia, and treatment-scope prompts before importing phenotype detail.