IEMbase 0023: HGD-related homogentisic acid oxidase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 23 |
| Nosology | 1.4.05.01 |
| Gene | HGD |
| External IDs | OMIM:203500 |
| Generated mapping | MAPPED by alias_exact:aku |
| Candidate DisMech targets | Alkaptonuria.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents classic alkaptonuria. The characteristic clinical triad is adult-onset arthritis, ochronosis, and urine darkening on standing, with urine darkening marked across all age bands. The defining biochemical signal is markedly elevated urinary homogentisate.
Additional IEMbase clinical signals include lumbosacral disc degeneration,
scleral pigmentation, general pigmentation, intrinsic dental staining, and adult
aortic and mitral valvulitis. No specific treatment rows are present in this
JSON record despite the disease-level treatability value being yes.
DisMech phenotype coverage
The generated mapping to Alkaptonuria.yaml is correct. DisMech covers HGD loss
of function, homogentisic acid accumulation and oxidation, ochronotic connective
tissue degeneration, dark urine, ochronosis, osteoarthritis/arthritis,
arthralgia, joint stiffness/swelling/dislocation, back pain, intervertebral disc
calcification, cartilage calcification/destruction, tendon rupture, Achilles
tendon thickening, aortic and mitral valve calcification/stenosis, coronary
calcification, nephrolithiasis, hearing abnormalities, visual/ocular
involvement, scleral and corneal-limbal pigmentation, skin pigmentation,
elevated urinary homogentisic acid, and reduced HGD activity. It also includes
nitisinone therapy.
Concordance and completeness
Judgement: correct mapping and very high concordance. DisMech is substantially richer than IEMbase for musculoskeletal, cardiovascular, renal, ocular, and treatment coverage.
IEMbase contributes a few useful granularity checks: intrinsic dental staining,
the explicit lumbosacral-disc wording, and inflammatory valvulitis labels.
DisMech already covers the same major organ systems, but mostly as calcific or
structural valve disease rather than valvulitis.
Curation actions
- Keep the generated mapping.
- Consider whether intrinsic dental staining merits a phenotype entry if supported by alkaptonuria evidence.
- Review whether the adult valve phenotype should stay framed as calcification or whether inflammatory valvulitis wording is evidence-supported.