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IEMbase 0555: AKR1C2-related 3-alpha-hydroxysteroid dehydrogenase type 3 deficiency

Scope

Field Value
IEMbase ID 555
Nosology 24.2.2.01
Gene AKR1C2
External IDs OMIM:600450; ORPHA:443087
Generated mapping UNMAPPED; best candidate Congenital_Adrenal_Hyperplasia.yaml#3B-HSD
Candidate DisMech targets No exact local target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents AKR1C2-related 3-alpha-hydroxysteroid dehydrogenase type 3 deficiency, with alternate labels aldoketoreductase 2 deficiency, backdoor pathway defect, and AKR1C. The record is autosomal recessive, and treatability is unknown. No treatment rows are listed.

The biochemical rows show markedly decreased urinary androsterone/etiocholanolone ratio and normal plasma testosterone. Clinical rows include ambiguous genitalia in 46,XY individuals, cryptorchidism, and adolescent/adult virilization.

DisMech phenotype coverage

No exact local AKR1C2 or backdoor androgen pathway target was found. The generated Congenital_Adrenal_Hyperplasia.yaml#3B-HSD candidate is not a valid match. That local subtype is HSD3B2-related adrenal steroidogenesis disease, whereas IEMbase describes AKR1C2-related 3-alpha-hydroxysteroid dehydrogenase type 3 deficiency with a diagnostic androsterone/etiocholanolone ratio.

Other local 46,XY DSD entries overlap at the phenotype level for ambiguous genitalia, but they do not provide AKR1C2 gene or backdoor pathway coverage.

Concordance and completeness

Judgement: true local disease gap; reject the CAH 3B-HSD candidate.

The IEMbase record is a gene-specific steroid backdoor pathway disorder with AKR1C2 identity, urinary steroid-ratio directionality, 46,XY undervirilization, cryptorchidism, and later virilization. It should not be treated as HSD3B2 congenital adrenal hyperplasia.

Curation actions

  • Keep this record unmapped until an AKR1C2 / 3-alpha-HSD type 3 deficiency target exists.
  • Do not map to Congenital_Adrenal_Hyperplasia.yaml#3B-HSD.
  • Preserve the androsterone/etiocholanolone ratio, normal testosterone, ambiguous genitalia in 46,XY, cryptorchidism, virilization, and backdoor pathway labels.