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IEMbase 0558: ATP13A2-related Kufor-Rakeb syndrome / CLN12

Scope

Field Value
IEMbase ID 558
Nosology 20.4.1.01
Gene ATP13A2
External IDs OMIM:606693; ORPHA:306674
Generated mapping UNMAPPED; best candidate Kufor-Rakeb_syndrome.yaml
Candidate DisMech targets Kufor-Rakeb_syndrome.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents ATP13A2-related lysosomal type 5 P-type ATPase deficiency, with alternate labels Kufor-Rakeb syndrome, Parkinson disease 9, and neuronal ceroid lipofuscinosis 12 / CLN12. The record is autosomal recessive, juvenile form, of unknown treatability, and has no treatment rows.

Clinical rows include cognitive dysfunction, dysarthria, electron-microscopy storage material, extrapyramidal movement disorder, gait disturbance, and neurodegenerative disease. Characteristic rows include akinesia, behavioral disorder, movement disorder, myoclonus, and rigidity.

DisMech phenotype coverage

Kufor-Rakeb_syndrome.yaml is the correct local target. It models autosomal recessive ATP13A2-related juvenile parkinsonism with spastic paraparesis, supranuclear eye movement abnormalities, progressive cognitive decline, and possible psychosis. The mechanism chain covers ATP13A2 loss, impaired lysosomal polyamine transport, lysosomal polyamine storage, secondary lysosomal hydrolase dysfunction, glucosylsphingosine accumulation, impaired mitochondrial quality control, and progressive neurodegeneration.

Local phenotypes include bradykinesia, rigidity, dystonia, spastic paraparesis, abnormal eye movement, facial myokymia, cognitive impairment, and psychiatric symptoms.

Concordance and completeness

Judgement: generated false negative; resolve to Kufor-Rakeb_syndrome.yaml.

IEMbase and DisMech agree on ATP13A2 identity, recessive inheritance, juvenile neurodegeneration, parkinsonian/extrapyramidal motor disease, rigidity, akinesia or bradykinesia, cognitive involvement, behavioral or psychiatric features, and lysosomal storage biology. DisMech is stronger for the polyamine-transport and lysosome-mitochondria mechanism.

IEMbase adds CLN12 and neuronal ceroid lipofuscinosis aliases, EM storage material, dysarthria, gait disturbance, and myoclonus prompts that are useful for aliasing and phenotype review.

Curation actions

  • Promote the IEMbase match to Kufor-Rakeb_syndrome.yaml.
  • Add or verify aliases for CLN12, neuronal ceroid lipofuscinosis 12, and ATP13A2-related lysosomal type 5 P-type ATPase deficiency.
  • Consider reviewing IEMbase-specific EM storage material, myoclonus, dysarthria, and gait-disturbance rows for possible phenotype additions.