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IEMbase 0570: HNF4A-related MODY1 with hyperinsulinism

Scope

Field Value
IEMbase ID 570
Nosology 24.1.05.01
Gene HNF4A
External IDs OMIM:600281; ORPHA:93111
Generated mapping UNMAPPED; best candidate Fanconi_Renotubular_Syndrome.yaml#FRTS4
Candidate DisMech targets Congenital_Isolated_Hyperinsulinism.yaml#HNF4A/HNF1A-HI; Diabetes_Mellitus.yaml#HNF4A; Fanconi_Renotubular_Syndrome.yaml#FRTS4 as variant-specific context only
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents HNF4A-related hepatocyte nuclear factor 4-alpha deficiency / MODY1. The record is autosomal dominant, idiopathic subtype, of unknown treatability, and has no treatment rows.

Biochemical rows include decreased free fatty acids during hypoglycemia, decreased ketones during hypoglycemia, low plasma glucose, and increased insulin during hypoglycemia. Clinical and characteristic rows include hypoglycemia, MODY1 diabetes, hyperinsulinism, hypoketotic hypoglycemia, and macrosomia.

DisMech phenotype coverage

Congenital_Isolated_Hyperinsulinism.yaml has a transcription-factor hyperinsulinism subtype for HNF4A/HNF1A variants, describing neonatal hyperinsulinism followed by maturity-onset diabetes later in life, often with macrosomia. Diabetes_Mellitus.yaml includes HNF4A as a causative monogenic diabetes gene. The generated Fanconi_Renotubular_Syndrome.yaml#FRTS4 candidate is variant-specific for HNF4A R76W/R85W renal Fanconi syndrome plus beta-cell phenotype, and should not be used as the primary target for a generic MODY1/hyperinsulinism IEMbase record.

Concordance and completeness

Judgement: generated false negative to the congenital hyperinsulinism and monogenic-diabetes neighborhood; reject Fanconi_Renotubular_Syndrome.yaml#FRTS4 as an exact mapping.

IEMbase and the local congenital hyperinsulinism entry agree on HNF4A, dominant inheritance, neonatal or early hyperinsulinism, hypoketotic hypoglycemia, macrosomia, and later MODY-type diabetes. Diabetes_Mellitus.yaml supports the HNF4A/MODY aspect but is broader than the IEMbase insulin- metabolism record.

Curation actions

  • Resolve the hyperinsulinism portion to Congenital_Isolated_Hyperinsulinism.yaml#HNF4A/HNF1A-HI.
  • Use Diabetes_Mellitus.yaml#HNF4A as monogenic-diabetes context, not as a complete gene-specific MODY1 entry.
  • Do not map this generic MODY1 record to FRTS4 unless the variant-specific Fanconi renal phenotype is present.