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IEMbase 0764: CYP2U1-related spastic paraplegia 56

Scope

Field Value
IEMbase ID 764
Nosology 14.5.01.14
Nosology code IEM0673
Gene CYP2U1
External IDs OMIM:615030; ORPHA:320411
Generated mapping CANDIDATE; Autosomal_Recessive_Cerebellar_Ataxia_With_Late_Onset_Spasticity.yaml
Candidate DisMech targets None exact
Review date 2026-07-08

IEMbase phenotype signal

IEMbase labels this autosomal recessive record as CYP2U1-related spastic paraplegia 56. The source signal includes characteristic spastic paraparesis, psychomotor retardation or regression, intellectual disability, dystonia, peripheral neuropathy, pigmentary maculopathy, thin corpus callosum, cerebellar white matter abnormalities, basal ganglia calcifications, and low-to-normal CSF 5-methyltetrahydrofolic acid in infancy and childhood.

DisMech phenotype coverage

No exact CYP2U1 / SPG56 entry is present locally. The generated Autosomal_Recessive_Cerebellar_Ataxia_With_Late_Onset_Spasticity.yaml candidate is a false positive for disease identity. That local entry is a GBA2-related SPG46 / cerebellar ataxia with late-onset spasticity disorder based on nonlysosomal glucosylceramidase deficiency, not CYP2U1-related SPG56.

Concordance and completeness

Judgement: true local gap.

The GBA2 candidate shares spasticity, ataxia, neuropathy, and corpus-callosum vocabulary, but it has the wrong causal gene and lipid mechanism. The IEMbase CYP2U1 record should remain unmapped until a SPG56-specific entry exists.

Curation actions

  • Add a distinct CYP2U1 / spastic paraplegia 56 target before treating this record as covered.
  • Reject Autosomal_Recessive_Cerebellar_Ataxia_With_Late_Onset_Spasticity.yaml as exact coverage.
  • Preserve the CSF 5-MTHF, basal-ganglia calcification, pigmentary maculopathy, thin corpus callosum, dystonia, neuropathy, and psychomotor regression prompts.