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IEMbase 0076: PNPO-related pyridoxamine 5-phosphate oxidase deficiency

Scope

Field Value
IEMbase ID 76
Nosology 21.6.01.01
Gene PNPO
External IDs OMIM:610090
Generated mapping UNMAPPED
Candidate DisMech targets Best fuzzy candidate COA3-Related_COX_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive PNPO-related pyridoxamine 5-phosphate oxidase deficiency, with alternate labels pyridoxal 5-phosphate dependent seizures and PNPO deficiency. Treatability is marked yes.

The characteristic biochemical signal includes abnormal CSF 5-hydroxyindoleacetic acid, CSF pyridoxal 5-phosphate, and plasma pyridoxamine. Additional biochemical rows include CSF 3-methoxytyrosine, CSF HVA, plasma and CSF threonine, plasma glycine, plasma lactate and glucose, vanillactic acid in urine, and the pyridoxamine/pyridoxic acid ratio.

The characteristic clinical row is pharmacoresistant seizures. Additional clinical rows include developmental delay, hypotonia, low Apgar scores, prematurity, and vomiting. The treatment row is pyridoxal 5-phosphate.

DisMech phenotype coverage

No valid local DisMech target was found for PNPO deficiency or pyridoxamine 5-phosphate oxidase deficiency.

The best fuzzy candidate, COA3-Related_COX_Deficiency.yaml, is a false positive. COA3-related COX deficiency is a mitochondrial complex IV assembly factor disorder with COA3/CCDC56, not a vitamin B6 cofactor-synthesis disorder. Local hypophosphatasia mentions extracellular pyridoxal 5-phosphate, but it is not PNPO deficiency.

Concordance and completeness

Judgement: true local gap.

This record is a treatable PLP-biosynthesis/cofactor disorder with pharmacoresistant neonatal or early-life seizures. It requires a separate PNPO entry rather than mapping to a mitochondrial COX assembly disease.

Curation actions

  • Keep this IEMbase record unmapped for now.
  • Add a future standalone PNPO deficiency entry.
  • Prioritize PLP-dependent seizure mechanism, CSF PLP and biogenic amine abnormalities, pyridoxamine/pyridoxic acid ratio, pharmacoresistant seizures, prematurity/low Apgar presentation, and PLP treatment.