Figure 1
Algorithm showing the approach to a suspected Wilson’s Disease patient. MRI: Magnetic resonance imaging; WD: Wilson disease.
Table 1
Dose, mechanism of action and important points regarding commonly used chelating agents in Wilson’s disease.
| MEDICATION | DOSE | MECHANISM OF ACTION | SIDE EFFECTS AND INTERACTIONS | REMARKS |
|---|---|---|---|---|
| D-penicillamine | 20 mg/kg/day (rounded to the nearest 250 mg). Slow escalation (preferably 250 mg alternate day in the beginning followed by increments of 250 mg every week to the target dose) | Copper chelator-enhances copper excretion through kidneys | Abdominal pain, Diarrhoea, Skin rashes Pyridoxine (25–50 mg/day) supplementation due to its anti-pyridoxine effect. | To be administered 1 hour before or 2 hours after meals Paradoxical worsening Has anti-pyridoxine effect |
| Trientine | 20 mg/kg/day (rounded to the nearest 300 mg) | Copper chelator-enhances copper excretion through kidneys | Nausea, Stomach pain, Joint pains Iron deficiency due to chelation effect | To be administered 1 hour before or 2 hours after meals Paradoxical worsening Monitor for iron deficiency |
| Zinc salts | 150 mg/day of elemental zinc in three divided doses | Inhibits the intestinal uptake of copper by inducing enterocyte metallothionein | Generally, it is well tolerated. Can have stomach pain, nausea | Not to take with food or with copper chelating agents. To be given with adequate spacing. Can have gastritis features Safe in pregnancy |
Table 2
Dose, mechanism of action and important points regarding commonly used symptomatic medications in Wilson’s disease.
| MEDICATION | DOSE | MECHANISM OF ACTION | REMARKS |
|---|---|---|---|
| Tremor | |||
| Propranolol | 40–240 mg/day in divided doses | Nonselective beta receptor antagonist | Monitor heart rate and blood pressure |
| Clonazepam | 0.5–4 mg/day | Direct effect on benzodiazepine receptor and facilitates GABAergic transmission in the brain | Can have excessive sedation with higher doses |
| Gabapentin | Start with a dose of 100–300 mg/d and slowly increase up to 1200–2400 mg/d in three divided doses or till tolerated | Action of presynaptic voltage-gated calcium channels and prevents the release of excitatory neurotransmitters | It may cause vision blurring, unsteadiness, and dizziness. |
| Primidone | Start 100–150 mg/d in 2–3 divided doses and titrate slowly up to 750 mg/d or till tolerated | Interacts with voltage-gated sodium channels and inhibits repetitive firing of action potentials | The rapid increase in dose can cause ataxia and depression. |
| Dystonia | |||
| THP | Start with 1 mg/day, slowly increase 1 mg every 3–5 days until optimal response is achieved/ side effects emerge | Muscarinic acetylcholine receptor antagonist | Few children may experience chorea Monitoring for dry mouth, constipation, and urinary retention. Contraindicated in narrow-angle glaucoma |
| Baclofen | Start with 5 mg/day, slowly increase 5 mg every 3–5 days to reach a maximum dose of 60 mg/day based on clinical response and side effects | Presynaptic GABA receptor agonist | Abrupt withdrawal can cause psychosis or seizures |
| Botulinum toxin | 25 to 200 units based on the type of dystonia and muscles involved. | Blocks the release of acetylcholine into the neuromuscular junction | Highly effective in focal and segmental dystonia. Can have transient weakness of injected muscles. |
| Parkinsonism | |||
| Levodopa | Start with 100 mg of levodopa (with carbidopa combination), and slowly increase one tablet every 3–5 days to reach optimal response or a maximum of 1200 mg/day | Converted to dopamine in presynaptic terminals of dopaminergic neurons, which further acts on postsynaptic dopamine receptors. | Administered with a combination of carboxylase inhibitor carbidopa. Monitor for nausea orthostasis with initial doses |
| Amantadine | 300 mg/day divided into 2–3 daily doses | The weak antagonist of NMDA-type glutamate receptors increases dopamine release and blocks dopamine reuptake. | Beneficial in patients with dyskinesias |
| Chorea | |||
| Tetrabenazine | Start with a 12.5 mg dose once daily, and slowly increase by 12.5 mg every 3–5 days to a target of 25–100 mg daily. | Depletes vesicular stores of dopamine by inhibiting the monoamine transporter-2 | Rapid increase in dosage can cause drowsiness, parkinsonism, depression, anxiety, and akathisia. |
[i] GABA: Gamma amino butyric acid; NMDA: N-methyl D-aspartate; THP: Trihexyphenidyl
Video 1
Video of Case-1 showing oro-mandibular dystonia, sialorrhea, distal predominant dystonia in all four limbs, lingual chorea, dysarthria, and worsening of dystonia on walking. The video was taken after written informed consent was obtained for video recording and publication in print and online.
Figure 2
A to C- MRI axial sections of Case-1 depicting T2 hyperintensities in bilateral thalamus (A), face of the giant panda sign in the midbrain (B), and face of the miniature panda sign in the pons (C). MRI: Magnetic resonance imaging.
Video 2
Video of Case-2 showing both upper and lower limb tremors (rest, posture with wing-beating quality) with dystonic posturing of both upper limb fingers. The video was taken after written informed consent was obtained for video recording and publication in print and online.
Video 3
Video of Case-3. Segment-1: Pre-operative video showing disabling rubral tremor in right upper limb with conducted tremor in left upper limb. Segment-2: 6-month follow-up video showing significant improvement of the tremor and functional ability after left ventral intermediate nucleus thalamotomy. The video was taken after written informed consent was obtained for video recording and publication in print and online.
Video 4
Video of Case-4 showing the presence of rest and postural tremors in a right upper limb with generalized dystonia with a dystonic smile and striatal toe in the left leg. The patient had presented to us with a worsening of her symptoms after initiating D-penicillamine. At the 3-month follow-up, there is a reduction of tremors after reducing the D-penicillamine dose with the persistence of dystonia and dystonic smile. The video was taken after written informed consent was obtained for video recording and publication in print and online.
Figure 3
Algorithm for screening of asymptomatic siblings of Wilson’s Disease patient. KF ring: Kayser–Fleischer ring; MRI: Magnetic resonance imaging; WD: Wilson disease.