IEMbase 0305: PPT1-related palmitoyl-protein thioesterase 1 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 305 |
| Nosology | 20.4.03.02 |
| Gene | PPT1 |
| External IDs | OMIM:256730; ORPHA:79263 |
| Generated mapping | MAPPED; Neuronal_Ceroid_Lipofuscinosis_1.yaml |
| Candidate DisMech targets | Neuronal_Ceroid_Lipofuscinosis_1.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents PPT1-related CLN1 disease as an infantile/childhood NCL with developmental regression, epilepsy, myoclonic seizures, movement disorder, muscular atrophy, microcephaly, maculopathy, retinopathy, cerebral 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, language difficulties, myoclonic epilepsy, myoclonus, neurodegenerative disease, optic atrophy, tonic-clonic seizures, abnormal somatosensory evoked potentials, spasticity, abnormal or delayed speech, spinal muscular atrophy, and abnormal VEP.
The biochemical row is specific and useful: markedly decreased lysosomal palmitoyl-protein thioesterase 1 activity in dried blood spots, fibroblasts, and white blood cells.
DisMech phenotype coverage
Neuronal_Ceroid_Lipofuscinosis_1.yaml is the correct local target. It models
PPT1 biallelic pathogenic variants, PPT1 lysosomal depalmitoylation failure,
autophagy suppression, lysosomal cholesterol homeostasis defects, and
AKAP5-NFAT synaptic neuroinflammatory signaling. Phenotype coverage includes
developmental regression, myoclonus, seizure, visual impairment, motor
deterioration, and mental deterioration. The file also includes an experimental
hematopoietic stem/progenitor cell gene therapy entry.
The local entry currently has no biochemical section, so the PPT1 enzyme
assay rows in IEMbase are not represented directly.
Concordance and completeness
Judgement: correct high-confidence mapping to
Neuronal_Ceroid_Lipofuscinosis_1.yaml.
Concordance is high for PPT1 gene identity, recessive NCL1 scope, developmental regression, seizures/myoclonus, progressive motor and cognitive decline, visual impairment, lysosomal storage biology, and neurodegeneration. DisMech is richer for molecular mechanism and model-based pathophysiology.
IEMbase is richer for clinical granularity, especially MRI/electrophysiology rows, optic atrophy versus generic visual impairment, maculopathy/retinopathy, spasticity/dystonia/ataxia, microcephaly, language or speech abnormality, and PPT1 enzyme activity across specimen types.
Curation actions
- Keep the generated NCL1 mapping.
- Add decreased PPT1 activity as a biochemical/diagnostic readout if supported by source evidence.
- Review granular neurologic, retinal, optic-atrophy, MRI, EEG/ERG/VEP, and speech-language rows for possible phenotype expansion.
- Treat spinal muscular atrophy and muscular atrophy rows cautiously, since they may need evidence before being modeled as core CLN1 phenotypes.