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IEMbase 0583: INSR-related insulin receptor dysregulation, Donohue syndrome

Scope

Field Value
IEMbase ID 583
Nosology 24.1.11.01
Gene INSR
External IDs OMIM:609968; ORPHA:769
Generated mapping UNMAPPED; best candidate IPEX_Syndrome.yaml
Candidate DisMech targets None exact
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents INSR-related insulin receptor dysregulation / Donohue syndrome, with alternate label familial hyperinsulinemic hypoglycemia type 5 / HHF5. The record is classified under disorders of insulin metabolism, lists autosomal dominant inheritance, has unknown treatability, and has no treatment rows.

Biochemical rows include decreased serum free fatty acids, decreased plasma or urinary ketones during hypoglycemia, decreased plasma glucose, and increased insulin during hypoglycemia. Clinical rows include hyperinsulinism and hyperpigmentation.

DisMech phenotype coverage

IPEX_Syndrome.yaml is a false-positive candidate. IPEX models FOXP3-related immune dysregulation with enteropathy, endocrinopathy, and eczema; it does not represent INSR, severe insulin receptoropathy, hyperinsulinemic hypoglycemia, suppressed ketogenesis, or free-fatty-acid suppression.

The local knowledge base has broad insulin-resistance, diabetes, and congenital hyperinsulinism context, and Donohue syndrome appears only as differential context elsewhere. No exact INSR/Donohue syndrome target was identified.

Concordance and completeness

Judgement: true local gap; reject IPEX syndrome as an exact mapping.

The IEMbase record is a receptor-signaling disorder centered on insulin action, hyperinsulinemia, hypoglycemia, suppressed ketone/free-fatty-acid physiology, and hyperpigmentation. It should not be merged into immune dysregulation or generic hyperinsulinism without preserving the INSR mechanism.

The IEMbase inheritance field should be source-reviewed during import because severe Donohue syndrome is commonly curated as a biallelic insulin-receptor disorder.

Curation actions

  • Create or identify an exact INSR severe insulin-receptoropathy / Donohue syndrome target before import.
  • Reject IPEX_Syndrome.yaml as an exact mapping.
  • Preserve the IEMbase hypoglycemia, high insulin, suppressed ketones, decreased free-fatty-acid, and hyperpigmentation prompts.
  • Source-review the IEMbase inheritance assertion before promoting it into DisMech.