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IEMbase 0651: HAAO-related 3-hydroxyanthranilic acid 3,4-dioxygenase deficiency

Scope

Field Value
IEMbase ID 651
Nosology 1.8.02.01
Nosology code IEM0163
Gene HAAO
External IDs OMIM:604521
Generated mapping UNMAPPED; weak candidate Alkaptonuria.yaml
Candidate DisMech targets No exact local target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive HAAO-related 3-hydroxyanthranilic acid 3,4-dioxygenase deficiency, also labeled vertebral, cardiac, renal, and limb defects syndrome type 1.

Biochemical rows include increased plasma 3-hydroxyanthranilic acid in neonatal and infantile ages, decreased plasma 3-hydroxyanthranilic acid in childhood, and decreased plasma NAD+. Clinical rows include atrial septal defect, hypoplastic left heart, optional intellectual disability, talipes, sensorineural hearing loss, renal hypoplasia, and short stature.

DisMech phenotype coverage

Alkaptonuria.yaml is a lexical/metabolic false candidate. It models HGD-related homogentisate 1,2-dioxygenase deficiency in tyrosine degradation, with homogentisic acid accumulation, ochronosis, dark urine, arthropathy, and nitisinone treatment. It does not model HAAO, the kynurenine pathway, NAD+ deficiency, or the vertebral/cardiac/renal/limb malformation syndrome.

Targeted search did not find a local HAAO, 3-hydroxyanthranilic acid dioxygenase, or VCRL type 1 disease entry.

Concordance and completeness

Judgement: true local HAAO / VCRL1 gap; reject alkaptonuria as exact.

The weak candidate shares the broad aromatic-amino-acid catabolism neighborhood but has the wrong gene, metabolite, mechanism, and clinical presentation. IEMbase supplies a distinct congenital malformation and NAD/kynurenine phenotype package that is not represented by existing DisMech entries.

Curation actions

  • Keep this row unmapped until a HAAO / VCRL type 1 target exists.
  • Do not map to Alkaptonuria.yaml.
  • Preserve 3-hydroxyanthranilic acid, NAD+, atrial septal defect, hypoplastic left heart, renal hypoplasia, talipes, hearing loss, short stature, and optional intellectual-disability prompts.