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IEMbase 0567: GLUD1-related hyperinsulinism-hyperammonemia syndrome

Scope

Field Value
IEMbase ID 567
Nosology 1.1.01.02
Gene GLUD1
External IDs OMIM:606762; ORPHA:35878
Generated mapping MAPPED; Congenital_Isolated_Hyperinsulinism.yaml#HI/HA Syndrome
Candidate DisMech targets Congenital_Isolated_Hyperinsulinism.yaml#HI/HA Syndrome
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents GLUD1-related glutamate dehydrogenase superactivity, with alternate labels hyperinsulinism-hyperammonemia syndrome and familial hyperinsulinemic hypoglycemia type 6. The record is autosomal dominant, idiopathic subtype, treatable, and lists diazoxide as a treatment.

Biochemical rows include decreased serum free fatty acids, decreased plasma and urinary ketones, normal-to-increased urinary 2-ketoglutaric acid, increased fasting ammonia, low plasma glucose, and increased plasma insulin. Clinical and characteristic rows include convulsions, abnormal EEG, intellectual disability, seizures, generalized epilepsy, hyperinsulinism, hypoglycemia, hypoketotic hypoglycemia, and leucine sensitivity causing hypoglycemia.

DisMech phenotype coverage

Congenital_Isolated_Hyperinsulinism.yaml#HI/HA Syndrome is the correct local target. The local subtype explicitly models dominant activating GLUD1 variants, glutamate dehydrogenase dysregulation, leucine/protein-sensitive hypoglycemia, persistent hyperammonemia, increased insulin secretion through beta-cell metabolic signaling, neurologic sequelae from hypoglycemia, and typical diazoxide responsiveness.

Concordance and completeness

Judgement: correct high-concordance subtype mapping to Congenital_Isolated_Hyperinsulinism.yaml#HI/HA Syndrome.

IEMbase and DisMech agree on GLUD1 identity, dominant inheritance, HI/HA scope, GDH superactivity, leucine sensitivity, hyperammonemia, hyperinsulinism, hypoketotic hypoglycemia, seizures/epilepsy, and diazoxide relevance. DisMech is stronger for the amino-acid-driven beta-cell mechanism and the convergence on insulin secretion.

IEMbase adds useful prompts for 2-ketoglutaric acid, EEG abnormality, generalized epilepsy, intellectual disability, and compartment-specific free fatty acid and ketone suppression.

Curation actions

  • Keep this record mapped to Congenital_Isolated_Hyperinsulinism.yaml#HI/HA Syndrome.
  • Consider reviewing IEMbase 2-ketoglutaric acid, EEG, generalized epilepsy, intellectual-disability, and compartment-specific ketone/free-fatty-acid rows for possible future phenotype or biochemical additions.
  • Preserve GLUD1/HHF6 aliases for matcher visibility.