IEMbase 0306: TPP1-related tripeptidyl-peptidase 1 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 306 |
| Nosology | 20.4.01.01 |
| Gene | TPP1 |
| External IDs | OMIM:204500; ORPHA:168491 |
| Generated mapping | MAPPED; Neuronal_Ceroid_Lipofuscinosis_2.yaml |
| Candidate DisMech targets | Neuronal_Ceroid_Lipofuscinosis_2.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents TPP1-related CLN2 disease with cerebral atrophy, developmental regression, movement disorder, optic atrophy, pigmentary retinopathy, retinal dystrophy, seizures, myoclonic seizures, spinal muscular atrophy, and vision loss or optic atrophy. Additional clinical rows include ataxia, cerebellar atrophy, cerebellar white matter abnormalities, dystonia, abnormal EEG, electron-microscopy storage material, abnormal ERG, muscular atrophy, myoclonic epilepsy, myoclonus, neurodegenerative disease, tonic-clonic seizures, abnormal somatosensory evoked potentials, spasticity, abnormal or delayed speech, and abnormal VEP.
Biochemical rows show markedly decreased lysosomal tripeptidyl-peptidase 1 activity in dried blood spots, fibroblasts, and white blood cells. Treatment is cerliponase alfa enzyme replacement.
DisMech phenotype coverage
Neuronal_Ceroid_Lipofuscinosis_2.yaml is the correct local target. It models
TPP1 biallelic pathogenic variants, TPP1 lysosomal peptidase deficiency,
progressive neurologic decline, progressive retinal degeneration, and the
classic two-to-four-year language delay/regression plus epilepsy presentation.
Phenotype coverage includes seizure, developmental regression, ataxia,
myoclonus, spasticity, dystonia, motor deterioration, visual impairment, and
retinal dystrophy.
Treatment coverage is strong: the file models intracerebroventricular cerliponase alfa enzyme replacement and AAVrh.10hCLN2 gene therapy. The local file does not currently model TPP1 enzyme activity as a biochemical readout.
Concordance and completeness
Judgement: correct high-confidence mapping to
Neuronal_Ceroid_Lipofuscinosis_2.yaml.
Concordance is high for TPP1 identity, late-infantile CLN2 scope, seizures, language/developmental regression, ataxia, myoclonus, spasticity, dystonia, motor decline, retinal dystrophy/visual loss, and cerliponase alfa treatment. DisMech is richer for progression, treatment mechanism, and separation of CNS and retinal degeneration.
IEMbase adds useful diagnostic and monitoring prompts: TPP1 activity assays by specimen, optic atrophy, pigmentary retinopathy, cerebral/cerebellar atrophy, white matter abnormality, EEG/ERG/VEP and somatosensory evoked-potential abnormalities, and abnormal speech. Muscular atrophy and spinal muscular atrophy should be checked carefully before import.
Curation actions
- Keep the generated NCL2 mapping.
- Add decreased TPP1 enzyme activity as a biochemical/diagnostic readout if source evidence supports specimen-specific rows.
- Review optic atrophy, pigmentary retinopathy, MRI, EEG/ERG/VEP, SSEP, and speech rows for phenotype expansion.
- Do not import muscular atrophy or spinal muscular atrophy rows without disease-specific evidence.