| Fenton reaction | Cu⁺ + H₂O₂ → Cu²⁺ + OH• + OH⁻ |
| Harber-Weiss reaction | Cu²⁺ + O₂•⁻ → Cu⁺ + O₂ |
| Mitochondrial complex IV inhibition | copper directly inhibits cytochrome c oxidase, impairing oxidative phosphorylation |
| Glutathione depletion | copper binds to reduced glutathione (GSH), depleting the primary cellular antioxidant |
| Alpha-synuclein aggregation | copper accelerates the misfolding and aggregation of alpha-synuclein, similar to mechanisms in Parkinson's disease |
| Ceruloplasmin oxidation | loss of functional ceruloplasmin reduces iron export, contributing to iron accumulation in the brain[@lorincz2010] |
| Chronic hepatitis | elevated ALT, AST, with or without symptoms |
| Cirrhosis | macronodular cirrhosis, portal hypertension |
| Fulminant hepatic failure | coagulopathy, hemolysis, jaundice. Occurs in 5-10% of patients, more common in females. Associated with Coombs-negative hemolytic anemia due to massive copper release[@schilsky1999] |
| Hepatocellular carcinoma | risk elevated in cirrhotic patients |
| Dystonia | the most common movement disorder, ranging from focal (blepharospasm, risus sardonicus) to generalized[@litwin2015] |
| Parkinsonism | bradykinesia, rigidity, tremor (resting or postural). Tremor is often "wing-beating" (proximal) |
| Databases | OMIMOrphanetClinicalTrialsPubMed |
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