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IEMbase 0124: H6PD-related Hexose-6-phosphate dehydrogenase deficiency

Scope

Field Value
IEMbase ID 124
Nosology 24.2.1.01
Gene H6PD
External IDs OMIM:604931; ORPHA:168588
Generated mapping MAPPED, high confidence
Candidate DisMech targets Cortisone_Reductase_Deficiency.yaml#Apparent CRD
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as H6PD-related hexose-6-phosphate dehydrogenase deficiency, with alternate labels cortisone reductase deficiency type 1 and CRD. Treatability is marked unknown.

The characteristic biochemical rows include increased ACTH, increased adrenal androgens, increased androstenedione, and a decreased urinary tetrahydrocortisol/tetrahydrocortisone ratio. Clinical rows include adrenal hyperplasia, precocious pseudopuberty in 46,XY individuals, and signs of androgen excess in women such as hirsutism. No treatment rows are listed.

DisMech phenotype coverage

Cortisone_Reductase_Deficiency.yaml includes an Apparent CRD subtype for H6PD variants that reduce endoplasmic-reticulum NADPH supply for 11-beta-HSD1 oxoreductase activity. The local entry describes impaired cortisone-to-cortisol regeneration, increased HPA drive, adrenal hyperandrogenism, premature adrenarche, precocious pseudopuberty, menstrual/reproductive dysfunction, and hirsutism.

The local mechanism and genetics cover H6PD directly. Treatment coverage includes dexamethasone adrenal androgen suppression.

Concordance and completeness

Judgement: correct mapping, with subtype resolution to apparent CRD.

DisMech captures the causal H6PD/11-beta-HSD1 cofactor mechanism and the main androgen-excess phenotype. IEMbase adds useful biochemical specificity for ACTH, androstenedione, adrenal androgens, and the urinary tetrahydrocortisol/tetrahydrocortisone ratio. The clinical overlap is strong for adrenal hyperplasia, precocious pseudopuberty, and hirsutism.

Curation actions

  • Keep Cortisone_Reductase_Deficiency.yaml#Apparent CRD as the target.
  • Consider adding explicit biochemical rows for ACTH, androstenedione, adrenal androgens, and urinary tetrahydrocortisol/tetrahydrocortisone ratio.
  • Review whether H6PD-specific rows should be distinguished from HSD11B1 true cortisone reductase deficiency rows in downstream subtype exports.