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IEMbase 0164: ASPA-related Canavan disease

Scope

Field Value
IEMbase ID 164
Nosology 1.9.01.03
Gene ASPA
External IDs OMIM:271900; ORPHA:314911
Generated mapping MAPPED to Canavan_Disease.yaml
Candidate DisMech targets Canavan_Disease.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as ASPA-related aspartoacylase deficiency, with alternate labels Canavan disease, N-acetylaspartic aciduria, and CD. Treatability is marked unknown.

The biochemical rows report increased N-acetylaspartic acid in CSF, plasma, and urine. The clinical rows include bilateral subcortical leukodystrophy, globus pallidus MRI abnormalities, macrocephaly, axial muscular hypotonia, spasticity, psychomotor retardation, intellectual disability, loss of very early milestones, blindness, optic atrophy, nystagmus, epilepsy, dysarthria, deafness, extrapyramidal movement disorder, decerebrate posture, and opisthotonus.

DisMech phenotype coverage

Canavan_Disease.yaml is the correct target. It models biallelic ASPA pathogenic variants, aspartoacylase deficiency, impaired hydrolysis of N-acetyl-L-aspartate, NAA accumulation in the central nervous system and body fluids, reduced NAA-derived acetate and myelin lipid synthesis, oligodendrocyte and myelination defects, spongiform white-matter vacuolation, macrocephaly, hypotonia, global developmental delay, visual impairment/blindness, optic atrophy, nystagmus, seizures, hypertonia/spasticity, developmental regression, feeding difficulty, supportive care, and investigational ASPA gene replacement or NAA-lowering strategies.

Concordance and completeness

Judgement: correct mapping with high concordance.

The IEMbase and DisMech profiles agree on ASPA/aspartoacylase deficiency, N-acetylaspartate accumulation, leukodystrophy, macrocephaly, hypotonia, developmental impairment/regression, optic/visual involvement, nystagmus, seizures, and spasticity. IEMbase adds compartment-specific CSF and plasma NAA rows, globus pallidus MRI abnormalities, bilateral subcortical leukodystrophy wording, decerebrate posture, opisthotonus, deafness, and extrapyramidal movement disorder as possible refinement targets.

The IEMbase ORPHA identifier differs from the local Canavan structured record used in DisMech; the disease identity is still correct through ASPA, OMIM 271900, and the Canavan/N-acetylaspartic aciduria labels.

Curation actions

  • Keep the mapping to Canavan_Disease.yaml.
  • Consider future biomarker refinement for CSF and plasma NAA in addition to urine and brain MRS.
  • Review whether IEMbase globus pallidus, decerebrate posture, opisthotonus, and extrapyramidal rows should be represented locally.
  • Check the ORPHA cross-reference difference during any future Canavan metadata cleanup.