| Lipid metabolism | C19orf12 is co-regulated with genes involved in fatty acid biosynthesis and lipid homeostasis. Loss of C19orf12 leads to altered lipid composition of mitochondrial membranes |
| ER-mitochondria communication | Disruption of MAM integrity impairs calcium transfer between the ER and mitochondria, affecting cell survival signaling |
| [Autophagy](/entities/autophagy) | C19orf12 deficiency leads to impaired autophagic flux, with accumulation of p62/SQSTM1 and ubiquitin-positive aggregates |
| Progressive spastic paraparesis | Lower limb spasticity with hyperreflexia and extensor plantar responses is often the earliest motor feature, distinguishing MPAN from other NBIA subtypes where extrapyramidal features predominate |
| Dystonia | Typically generalized, progressive, and often severe; may be focal at onset before generalizing |
| Parkinsonism | Bradykinesia and rigidity develop with disease progression; tremor is less prominent than in Parkinson's disease |
| Cognitive decline | Progressive intellectual deterioration, often with prominent executive dysfunction and eventually global dementia |
| Psychiatric features | Depression, anxiety, emotional lability, impulsivity, and psychotic symptoms including visual hallucinations occur in up to 50% of patients (Hogarth et al., 2013) |
| Optic atrophy | Present in approximately 60% of patients; leads to progressive visual loss |
| Motor axonal neuropathy | Distal weakness and muscle wasting due to motor neuron involvement; distinguishes MPAN from other NBIA subtypes |
| Dysarthria and dysphagia | Progressive bulbar dysfunction |
| Iron deposition | Heavy iron accumulation in the globus pallidus (particularly the medial segment) and substantia nigra, with iron deposits in both neurons and glia |
| Databases | OMIMOrphanetClinicalTrialsPubMed |
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