Challenges and dilemmas in pediatric hepatic Wilson’s disease

Table 5 Drugs, their mechanism of action, dosage and side effects

Name of drug	Mechanism of action	Dose	When to start	Side effects
D-penicillamine	Induces cuprieuresis, induces hepatic metallothionine synthesis, reduces fibrosis (by preventing collagen formation)	20 mg/kg/d (maximum induction dose of 1500 mg/d and maintenance dose of 1000 mg/d), to be taken 1 h before or 2 h after meal, storage at room temperature	Chelator of choice in all hepatic phenotype	Early (1-3 wk): Fever, rash, arthralgia, cytopenia, proteinuria; Late: (1) Skin: degenerative dermatoses elastosis perforans serpingosa, cutis laxa, pseudoxanthoma elasticum, bullous dermatoses, psoriasiform dermatoses, lichen planus, seborrheic dermatitis alopecia, aphthous ulcerations, hair loss; (2) Connective tissue disorders: Lupus like syndrome, arthralgia, Rheumatoid arthritis, polymyositis; (3) Renal: proteinuria, hematuria, glomerulonephritis, nephrotic syndrome, renal vasculitis, Goodpasture’s syndrome; (4) Nervous system: Paradoxical neurological worsening, neuropathies, myasthenia, hearing abnormalities, serous retinitis; (5) Gastrointestinal: Nausea, vomiting, diarrhea, elevated transaminases, cholestasis, hepatic siderosis; (6) Respiratory: Pneumonitis, pulmonary fibrosis, pleural effusion; (7) Hematological: Cytopenia, agranulocytosis, aplastic anemia, hemolytic anemia; and (8) Others: Immunoglobulin deficiency, breast enlargement, pyridoxine deficiency
Trientine	Induces cuprieuresis, induces hepatic metallothionine synthesis	20 mg/kg/d (maximum induction dose of 1500 mg/d and maintenance dose of 1000 mg/d), to be taken 1 h before or 2 h after meal, storage at 20-80 temperature	Indicated if intolerant to D-penicillamine	Paradoxical neurological worsening (10%-50%), sideroblastic anemia, bone marrow suppression, gastritis, skin rash, arthralgia, myalgia, hirsutism
Zinc	Induces intestinal synthesis of metallothioneins, prevents copper absorption	25 mg thrice daily (weight < 50 kg), 50 mg thrice daily (weight > 50 kg), taken in empty stomach	Maintenance phase of symptomatic hepatic WD; First-line induction treatment in selected patient subgroups (neurologic WD, intolerant to chelators, pre-symptomatic patients)	Gastric irritation (30%-40%)
Ammonium Tetra-thiomolybdate	Forms complexes with copper in blood, binds the copper present in food		Neurological WD	Neurological dysfunction (rare), hepatotoxicity, bone marrow suppression

WD: Wilson disease.