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IEMbase 0652: KYNU-related 3-hydroxykynureninase deficiency

Scope

Field Value
IEMbase ID 652
Nosology 1.8.01.02
Nosology code IEM0162
Gene KYNU
External IDs OMIM:605197; ORPHA:79155
Generated mapping UNMAPPED; weak candidate Hereditary_Orotic_Aciduria.yaml
Candidate DisMech targets No exact local target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive KYNU-related 3-hydroxykynureninase deficiency, with alternate labels vertebral, cardiac, renal, and limb defects syndrome type 2 and xanthurenic aciduria.

Biochemical rows include increased urinary 3-hydroxykynurenine, kynurenine, and xanthurenic acid; increased plasma 3-hydroxykynurenine; and decreased plasma NAD+. Clinical rows include anteriorly placed anus, hypoplastic left heart, patent ductus arteriosus, rhizomelia, abnormal/delayed/absent speech, syndactyly, renal hypoplasia, short stature, and talipes.

DisMech phenotype coverage

Hereditary_Orotic_Aciduria.yaml is a lexical false candidate. It models UMPS-related de novo pyrimidine synthesis failure, urinary orotic acid, megaloblastic anemia, developmental delay, and uridine responsiveness. It does not model KYNU, kynurenine-pathway flux, xanthurenic aciduria, NAD+ deficiency, or the VCRL2 malformation pattern.

Targeted search did not find a local KYNU, 3-hydroxykynureninase deficiency, xanthurenic aciduria, or VCRL type 2 disease entry.

Concordance and completeness

Judgement: true local KYNU / VCRL2 gap; reject hereditary orotic aciduria as exact.

The generated candidate is an unrelated nucleotide-metabolism disorder. IEMbase points to a separate tryptophan/kynurenine-pathway malformation disorder with specific metabolite readouts and cardiac/renal/limb/developmental prompts.

Curation actions

  • Keep this row unmapped until a KYNU / VCRL type 2 target exists.
  • Do not map to Hereditary_Orotic_Aciduria.yaml.
  • Preserve increased 3-hydroxykynurenine, kynurenine, xanthurenic acid, decreased NAD+, congenital heart findings, renal hypoplasia, rhizomelia, syndactyly, talipes, anteriorly placed anus, short stature, and speech prompts.