Table 1. Comparison between Wilson disease, AHD, and Chronic Manganism.

	Wilson Disease	AHD	Chronic Manganism
Etiology or risk factors	Causative gene: ATP7B (Family history)	Chronic liver failure, portosystemic shunt	Occupational exposures: welders, miners
Possible pathomechanism	Accumulation of copper	Synergistic actions of multiple mechanisms Accumulation of toxic substances: ammonia, manganese Neuroinflammation Oxidative and nitrosative stress	Accumulation of manganese
Clinical characteristics	Age at onset: <30 Ophthalmic: K-F rings Hepatic: hepatic dysfunction Movement disorders: parkinsonism, dystonia, wing-beating tremor, ataxia, dysarthria, and chorea Cognition: impaired executive function and attention deficits Psychiatric: depression, personality changes, psychosis	Age at onset: variable Ophthalmic: absence of K-F ring Hepatic: advanced hepatobiliary diseases Movement disorders: ataxia, tremor, parkinsonism, chorea, dystonia, and myoclonus Cognition: inattentiveness, apathy, and psychomotor slowness Psychiatric: apathy, disinhibition, aggression	Age at onset: variable, mostly adulthood Ophthalmic: absence of K-F ring Hepatic: normal function Movement disorders: parkinsonism, dystonia, and gait disturbance Cognitive dysfunction Psychiatric changes: compulsive behaviors, psychosis
Laboratory findings	Serum ceruloplasmin: ↓ 24-hour urinary copper: ↑ Abnormal liver function tests Hemolytic anemia: present Genetic testing: ATP7B mutations	Abnormal liver function tests Normal to slightly increased ammonia level Increased manganese levels in whole blood and CSF may be shown	Increased manganese levels in whole blood
Neuroimaging findings	T2-MRI (m/c): hyperintensities in the thalamus, lentiform and caudate nuclei, midbrain (“face of the giant panda”), and cerebellum T1-MRI: hyperintensities in the globus pallidus	T1-MRI (m/c): hyperintensities in the globus pallidus, putamen, and substantia nigra T2-MRI: MCP and cerebellum F-DOPA and DAT scan: conflicting results (normal uptake and reduced uptake of F-DOPA and DAT)	T1-MRI hyperintensities in the globus pallidus and substantia nigra F-DOPA and DAT scan: conflicting results (normal uptake and reduced uptake of F-DOPA and DAT)
Pathology	Opalski cells, Alzheimer type II astrocyte, cavitations	Alzheimer type II astrocyte, polymicrocavitation, CPM/EPM	Alzheimer type II astrocyte
Management	Chelating agent: zinc, penicillamine, trientine (effective) Hepatic failure: liver transplantation (controversial) Symptomatic therapy Parkinsonism: levodopa (may be beneficial) Tremor: beta-blocker Dystonia: anticholinergics, botulinum toxin	No established treatments Liver transplantation for liver failure (may reverse neurologic manifestations) Symptomatic therapy: Parkinsonism: levodopa (may be beneficial) Tremor: beta-blocker, anticholinergics (limited) Chorea: tetrabenazine (limited) Other treatments: trientine, BCAA, and BRTO (controversial)	Chelating agent: CaNa2EDTA, PAS Symptomatic therapy: Parkinsonism: levodopa (limited)

Abbreviations: BCAA, Branched-Chain Amino Acid; BRTO, Balloon-Occluded Retrograde Transvenous Obliteration; CaNa₂EDTA, Calcium Disodium Salt Ethylene Diamine Tetraacetic Acid; CPM, Central Pontine Myelinolysis; CSF, Cerebrospinal Fluid; DAT, Dopamine Transporter; EPM, Extrapontine Myelinolysis; F-DOPA, Fluorodopa; K-F rings, Kayser-Fleischer Rings; MCP, Middle Cerebellar Peduncles; m/c, Most Common; PAS, Para-Aminosalicylic Acid; T1-MRI, T1-Weighted Magnetic Resonance Imaging; T2-MRI, T2-Weighted Magnetic Resonance Imaging.