Wilson's Disease¶
VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 30, 2026 STATUS: Approved
DIAGNOSIS: Wilson's Disease (Hepatolenticular Degeneration)
ICD-10: E83.01 (Wilson's disease), E83.09 (Other disorders of copper metabolism), G25.5 (Other chorea — for movement disorder presentation), G25.2 (Other specified forms of tremor — for tremor-predominant presentation), F06.8 (Other specified mental disorders due to known physiological condition — psychiatric presentation)
CPT CODES: 82390 (Serum ceruloplasmin), 82525 (Serum copper (total)), 85025 (CBC with differential), 80053 (CMP (BMP + LFTs)), 82248 (Direct and indirect bilirubin), 85610 (PT/INR), 85045 (Reticulocyte count), 86880 (Direct Coombs test (DAT)), 83010 (Haptoglobin), 83615 (LDH), 81003 (Urinalysis), 84100 (Phosphorus), 84550 (Uric acid), 82947 (Blood glucose), 81406 (ATP7B gene sequencing), 85060 (Peripheral blood smear), 82140 (Ammonia level), 83605 (Lactate), 82105 (Alpha-fetoprotein (AFP)), 80074 (Hepatitis panel (HAV, HBV, HCV)), 86235 (ANA, anti-smooth muscle antibody), 83540 (Iron studies), 84443 (TSH), 82607 (Vitamin B12), 86255 (Paraneoplastic antibody panel), 77080 (Bone densitometry (DEXA)), 70551 (MRI brain without contrast), 70553 (MRI brain with contrast), 76700 (Abdominal ultrasound with Doppler), 71046 (Chest X-ray), 74178 (CT abdomen with contrast), 74183 (MRI abdomen (liver)), 91200 (FibroScan (transient elastography)), 43239 (Upper endoscopy (EGD)), 93000 (ECG (12-lead)), 93306 (Echocardiogram), 95816 (EEG), 78608 (PET brain (FDG)), 76390 (MR spectroscopy (brain)), 78830 (DaTscan), 47000 (Liver biopsy)
SYNONYMS: Wilson disease, WD, hepatolenticular degeneration, progressive lenticular degeneration, Westphal-Strümpell pseudosclerosis, copper storage disease, ATP7B deficiency, hepatocerebral degeneration, Wilson's, copper overload disease, hepatolenticular syndrome, Kinnier Wilson disease
SCOPE: Diagnosis and management of Wilson's disease in adolescents and adults presenting with neurologic, hepatic, or psychiatric manifestations. Covers diagnostic workup (ceruloplasmin, 24-hour urine copper, slit-lamp exam, hepatic copper, genetic testing), chelation therapy (D-penicillamine, trientine), zinc maintenance therapy, liver transplant evaluation, symptomatic management of neurological symptoms (dystonia, tremor, parkinsonism, psychiatric), and family screening. Excludes other copper metabolism disorders (Menkes disease), isolated non-Wilson hepatic cirrhosis, and drug-induced movement disorders.
DEFINITIONS: - Wilson's Disease (WD): Autosomal recessive disorder caused by mutations in the ATP7B gene (chromosome 13q14.3), resulting in defective copper excretion into bile and incorporation into ceruloplasmin, leading to toxic copper accumulation in liver, brain, cornea, kidneys, and other organs - Kayser-Fleischer (KF) Rings: Golden-brown deposits of copper in the Descemet membrane of the cornea; detected by slit-lamp exam; present in >95% of neurologic WD and ~50% of hepatic-only WD - Wing-Beating Tremor: Coarse, irregular, proximal tremor elicited with arms outstretched and elbows flexed; characteristic (though not pathognomonic) of WD - Ceruloplasmin: Copper-carrying glycoprotein synthesized in the liver; typically low (<20 mg/dL) in WD but can be normal in 5-15% of neurologic WD - Free (Non-ceruloplasmin-bound) Copper: Calculated as total serum copper minus ceruloplasmin-bound copper; elevated in WD (>25 mcg/dL) - Leipzig Score: Diagnostic scoring system for WD incorporating KF rings, neurologic symptoms, ceruloplasmin, Coombs-negative hemolytic anemia, hepatic copper, urinary copper, and mutation analysis (score ≥4 = established diagnosis)
KEY CLINICAL FEATURES:
Neurologic Manifestations (40-50% of presentations): - Movement disorders: Dystonia (most common neurologic feature), tremor (resting, postural, wing-beating), parkinsonism, choreoathetosis, athetosis - Bulbar symptoms: Dysarthria (most common initial neurologic symptom), dysphagia, drooling, dysphonia - Gait disturbance: Ataxia, postural instability - Other: Seizures (rare, 6%), risus sardonicus (fixed grin from facial dystonia)
Hepatic Manifestations (40-50% of presentations): - Asymptomatic transaminase elevation - Chronic hepatitis - Cirrhosis (compensated or decompensated) - Fulminant hepatic failure (with Coombs-negative hemolytic anemia)
Psychiatric Manifestations (30-40%, often earliest): - Depression, anxiety - Personality change, irritability - Psychosis (rare) - Cognitive decline, declining school/work performance - Behavioral disinhibition
Other Manifestations: - Ophthalmologic: KF rings, sunflower cataracts - Hematologic: Coombs-negative hemolytic anemia - Renal: Fanconi syndrome, renal tubular acidosis, nephrolithiasis - Musculoskeletal: Osteoporosis, arthropathy - Cardiac: Cardiomyopathy (rare)
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════
1. LABORATORY WORKUP¶
1A. Essential/Core Labs¶
| Test | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| Serum ceruloplasmin (CPT 82390) | URGENT | STAT | ROUTINE | STAT | Low in 85-95% of WD; screening test; may be normal in acute liver failure or inflammation | <20 mg/dL (often <10 mg/dL in WD); normal does NOT exclude WD |
| Serum copper (total) (CPT 82525) | URGENT | STAT | ROUTINE | STAT | Low-normal total copper (paradoxically) but elevated free copper in WD | Total copper low-normal (40-80 mcg/dL); calculate free copper |
| 24-hour urine copper (CPT 82525) | - | STAT | ROUTINE | STAT | Gold standard screening; elevated in WD; >100 mcg/24h suggestive; >40 mcg/24h in children | >100 mcg/24h (often >200 in symptomatic WD); normal <40 mcg/24h |
| CBC with differential (CPT 85025) | STAT | STAT | ROUTINE | STAT | Coombs-negative hemolytic anemia; baseline; thrombocytopenia (hypersplenism) | Hemolytic anemia, thrombocytopenia suggest WD |
| CMP (BMP + LFTs) (CPT 80053) | STAT | STAT | ROUTINE | STAT | AST/ALT elevation; synthetic function (albumin, bilirubin); renal function | Elevated AST/ALT (often AST > ALT); low albumin; elevated bilirubin in advanced disease |
| Direct and indirect bilirubin (CPT 82248) | STAT | STAT | ROUTINE | STAT | Elevated indirect bilirubin in hemolysis; elevated direct in hepatic disease | Elevated (especially indirect if hemolysis) |
| PT/INR (CPT 85610) | STAT | STAT | ROUTINE | STAT | Hepatic synthetic function; coagulopathy in liver failure | Elevated INR in advanced disease; INR >1.5 suggests significant hepatic dysfunction |
| Reticulocyte count (CPT 85045) | URGENT | STAT | ROUTINE | STAT | Elevated in hemolytic anemia | Elevated (>2%) suggests active hemolysis |
| Direct Coombs test (DAT) (CPT 86880) | URGENT | STAT | ROUTINE | STAT | NEGATIVE in WD hemolysis (Coombs-negative hemolytic anemia is classic) | Negative (positive Coombs suggests other etiology) |
| Haptoglobin (CPT 83010) | URGENT | STAT | ROUTINE | STAT | Low/undetectable in hemolysis | Low or undetectable in active hemolysis |
| LDH (CPT 83615) | URGENT | STAT | ROUTINE | STAT | Elevated in hemolysis | Elevated in hemolysis |
| Urinalysis (CPT 81003) | STAT | STAT | ROUTINE | STAT | Renal tubular dysfunction (glycosuria, proteinuria, aminoaciduria — Fanconi syndrome) | Glycosuria with normal serum glucose; proteinuria |
| Phosphorus (CPT 84100) | STAT | STAT | ROUTINE | STAT | Hypophosphatemia from renal tubular loss | Low (Fanconi syndrome) |
| Uric acid (CPT 84550) | - | ROUTINE | ROUTINE | ROUTINE | Low uric acid suggests renal tubular dysfunction | Low (<2 mg/dL suggests renal copper toxicity) |
| Blood glucose (CPT 82947) | STAT | STAT | ROUTINE | STAT | Baseline; glycosuria with normal glucose suggests Fanconi | Normal (but glycosuria present = renal tubular) |
1B. Extended Workup (Second-line)¶
| Test | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| Free (non-ceruloplasmin-bound) copper (calculated) | - | STAT | ROUTINE | STAT | Calculated: total serum copper (mcg/dL) minus (3 x ceruloplasmin [mg/dL]); elevated in WD | >25 mcg/dL (often >50 in symptomatic WD); most specific biochemical marker |
| Penicillamine challenge test (24-hour urine copper after 500 mg penicillamine x 2 doses) | - | ROUTINE | ROUTINE | - | Used in equivocal cases, especially pediatric; less validated in adults | >1600 mcg/24h highly suggestive of WD (>25 mcmol/24h) |
| ATP7B gene sequencing (CPT 81406) | - | ROUTINE | ROUTINE | - | Definitive diagnosis; identifies pathogenic variants; essential for family screening | Two pathogenic variants = confirmed WD; one variant + clinical findings = probable WD |
| Peripheral blood smear (CPT 85060) | URGENT | STAT | ROUTINE | STAT | Schistocytes, spherocytes in hemolytic anemia | Fragmented RBCs, polychromasia |
| Ammonia level (CPT 82140) | STAT | STAT | - | STAT | Hepatic encephalopathy assessment in liver failure | Normal <35 mcmol/L; elevated in hepatic failure |
| Lactate (CPT 83605) | STAT | STAT | - | STAT | Tissue hypoperfusion in fulminant hepatic failure | Elevated in liver failure |
| Alpha-fetoprotein (AFP) (CPT 82105) | - | ROUTINE | ROUTINE | - | HCC screening in cirrhotic patients | Normal; elevated suggests HCC |
| Hepatitis panel (HAV, HBV, HCV) (CPT 80074) | - | ROUTINE | ROUTINE | - | Exclude concurrent viral hepatitis | Negative |
| ANA, anti-smooth muscle antibody (CPT 86235) | - | ROUTINE | ROUTINE | - | Exclude autoimmune hepatitis (may coexist or mimic) | Negative or low titer |
| Iron studies (CPT 83540) | - | ROUTINE | ROUTINE | - | Exclude hemochromatosis in hepatic presentation | Normal ferritin and transferrin saturation |
| TSH (CPT 84443) | - | ROUTINE | ROUTINE | - | Thyroid dysfunction can present with tremor/psychiatric symptoms | Normal |
| Vitamin B12 (CPT 82607) | - | ROUTINE | ROUTINE | - | B12 deficiency can cause neuropsychiatric symptoms | Normal |
1C. Rare/Specialized (Refractory or Atypical)¶
| Test | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| Hepatic copper concentration (liver biopsy) (CPT 82525) | - | ROUTINE | ROUTINE | - | Gold standard for diagnosis; required when non-invasive testing equivocal; >250 mcg/g dry weight diagnostic | >250 mcg/g dry weight (normal <50 mcg/g); values 50-250 can be seen in heterozygotes or cholestatic disease |
| Radioactive copper incorporation study (⁶⁴Cu or ⁶⁷Cu) | - | EXT | EXT | - | Measures copper incorporation into ceruloplasmin over 48h; absent second peak in WD; rarely available | Absent secondary rise at 48h (failure of copper incorporation into ceruloplasmin) |
| Relative exchangeable copper (REC) ratio | - | EXT | EXT | - | Emerging biomarker; ratio of exchangeable copper to total copper; highly sensitive/specific | >18.5% diagnostic of WD |
| Paraneoplastic antibody panel (CPT 86255) | - | EXT | EXT | - | If atypical neurologic features not explained by WD alone | Negative |
| Heavy metal screen (lead, mercury, arsenic) | - | EXT | EXT | - | Toxic metal exposure can cause neuropsychiatric symptoms | Normal |
| Urine amino acids | - | EXT | EXT | - | Fanconi syndrome confirmation (generalized aminoaciduria) | Elevated (generalized aminoaciduria in Fanconi) |
| Bone densitometry (DEXA) (CPT 77080) | - | - | ROUTINE | - | Osteoporosis screening; copper toxicity causes bone loss | T-score > -2.5 |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line¶
| Study | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| Slit-lamp examination (ophthalmology) | URGENT | STAT | ROUTINE | STAT | At initial evaluation; do NOT rely on naked-eye exam | Kayser-Fleischer rings (present in >95% neurologic WD, ~50% hepatic-only); sunflower cataracts | None |
| MRI brain without contrast (CPT 70551) | URGENT | URGENT | ROUTINE | URGENT | Within 24-48h if neurologic symptoms | T2/FLAIR hyperintensity in basal ganglia (putamen — "face of the giant panda" sign on midbrain), thalamus, caudate, brainstem, cerebellum, white matter; T1 hyperintensity (copper/manganese deposition); cerebral atrophy | Pacemaker, metallic implants |
| MRI brain with contrast (CPT 70553) | - | ROUTINE | ROUTINE | - | If additional characterization needed | Rarely enhances; helps exclude other pathology | Contrast allergy, GFR <30 |
| Abdominal ultrasound with Doppler (CPT 76700) | URGENT | STAT | ROUTINE | STAT | At diagnosis | Hepatomegaly, splenomegaly, cirrhotic changes, portal hypertension, ascites | None significant |
| Chest X-ray (CPT 71046) | URGENT | ROUTINE | - | STAT | On admission for fulminant hepatic failure; baseline for ICU | Aspiration, atelectasis, pleural effusion, pulmonary edema | None significant |
2B. Extended¶
| Study | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| CT abdomen with contrast (CPT 74178) | - | ROUTINE | ROUTINE | - | If ultrasound equivocal; HCC screening | Cirrhosis, portal hypertension, hepatic lesions | Contrast allergy, renal impairment |
| MRI abdomen (liver) (CPT 74183) | - | ROUTINE | ROUTINE | - | Liver characterization; iron vs copper deposition | Hepatic signal abnormalities; excludes HCC | Per MRI |
| FibroScan (transient elastography) (CPT 91200) | - | - | ROUTINE | - | Non-invasive fibrosis assessment | Liver stiffness <7.1 kPa = minimal fibrosis; >12.5 kPa = cirrhosis | Ascites, obesity (limited), pacemaker |
| Upper endoscopy (EGD) (CPT 43239) | - | ROUTINE | ROUTINE | - | Variceal screening in cirrhotic patients | No varices; if present, grade and treat | Active GI perforation |
| ECG (12-lead) (CPT 93000) | URGENT | ROUTINE | ROUTINE | URGENT | Baseline; cardiac involvement | Arrhythmias, conduction abnormalities | None |
| Echocardiogram (CPT 93306) | - | ROUTINE | ROUTINE | - | If cardiac symptoms or cardiomyopathy suspected | Normal function; WD cardiomyopathy rare | None significant |
| NCS/EMG (CPT 95907-95913 / 95886) | - | - | ROUTINE | - | If peripheral neuropathy suspected | Rule out concurrent neuropathy | None significant |
| EEG (CPT 95816) | URGENT | ROUTINE | - | URGENT | If seizures suspected or encephalopathy | Generalized slowing in encephalopathy; epileptiform discharges | None |
2C. Rare/Specialized¶
| Study | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| PET brain (FDG) (CPT 78608) | - | - | EXT | - | If atypical features or diagnostic uncertainty | Hypometabolism in basal ganglia, cerebellum | Per PET |
| MR spectroscopy (brain) (CPT 76390) | - | EXT | EXT | - | Research; metabolic characterization | Reduced NAA (neuronal loss) in basal ganglia | Per MRI |
| DaTscan (CPT 78830) | - | - | EXT | - | Differentiate WD parkinsonism from idiopathic PD if uncertain | May show reduced uptake (presynaptic dopaminergic loss); less specific in WD | Pregnancy, iodine allergy |
| Liver biopsy (CPT 47000) | - | ROUTINE | ROUTINE | - | When non-invasive testing equivocal; hepatic copper quantification | Copper >250 mcg/g dry weight = diagnostic; histology shows steatosis, hepatitis, cirrhosis | Coagulopathy (INR >1.5), ascites (use transjugular), thrombocytopenia |
3. TREATMENT¶
3A. Acute/Emergent¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| N-acetylcysteine (NAC) | IV | Fulminant hepatic failure; hepatoprotection | 150 mg/kg :: IV :: loading :: 150 mg/kg IV over 1h, then 50 mg/kg over 4h, then 100 mg/kg over 16h (standard NAC protocol for liver failure) | None absolute | Anaphylactoid reaction, bronchospasm; monitor LFTs, INR | STAT | STAT | - | STAT |
| Fresh frozen plasma (FFP) | IV | Coagulopathy in fulminant hepatic failure | 10-15 mL/kg :: IV :: PRN :: 10-15 mL/kg IV; target INR <1.5 for procedures; use as bridge to transplant | Volume overload; IgA deficiency | INR, fibrinogen, volume status | STAT | STAT | - | STAT |
| Vitamin K (phytonadione) | IV | Coagulopathy; hepatic synthetic failure | 10 mg :: IV :: daily :: 10 mg IV daily x 3 days; limited efficacy in WD fulminant failure (hepatocyte loss) | Allergy | INR response | STAT | STAT | - | STAT |
| Lactulose | PO | Hepatic encephalopathy | 30 mL :: PO :: TID :: 30 mL PO TID; titrate to 3-4 bowel movements/day | Bowel obstruction | Mental status, ammonia, stool output | STAT | STAT | - | STAT |
| Rifaximin | PO | Hepatic encephalopathy (adjunct to lactulose) | 550 mg :: PO :: BID :: 550 mg PO BID; add if lactulose alone insufficient | C. difficile (relative) | Mental status, hepatic function | - | ROUTINE | - | ROUTINE |
| Albumin (25%) | IV | Ascites management; hepatorenal syndrome | 1 g/kg :: IV :: daily :: 1 g/kg/day (max 100 g); for large-volume paracentesis or hepatorenal syndrome | Heart failure | Volume status, serum albumin | - | STAT | - | STAT |
| Platelet transfusion | IV | Thrombocytopenia with active bleeding or pre-procedure | Dose per protocol :: IV :: PRN :: 1 unit apheresis platelets; target >50K for procedures, >10K if no bleeding | ITP, TTP (relative) | Platelet count post-transfusion | STAT | STAT | - | STAT |
| Plasmapheresis/Plasma exchange | Extracorporeal | Fulminant WD with severe hemolysis; removes free copper | 1-1.5 plasma volumes :: Extracorporeal :: daily :: Daily exchange x 3-5 days; rapidly reduces free copper | Hemodynamic instability, severe sepsis | Copper levels, hemolysis markers, coagulation | - | STAT | - | STAT |
| DVT prophylaxis: Enoxaparin | SC | Immobilized hospitalized patients | 40 mg :: SC :: daily :: 40 mg SC daily; hold if INR >1.5 or platelets <50K or active bleeding | Active bleeding, severe coagulopathy, CrCl <30 (use UFH) | Platelets, signs of bleeding | - | ROUTINE | - | ROUTINE |
3B. Symptomatic Treatments¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Baclofen | PO | Dystonia, spasticity | 5 mg :: PO :: TID :: Start 5 mg TID; titrate by 5 mg/dose every 3 days; target 30-80 mg/day divided TID; max 80 mg/day | Severe renal impairment; abrupt withdrawal risk | Sedation, weakness; do NOT stop abruptly (withdrawal seizures) | - | ROUTINE | ROUTINE | ROUTINE |
| Trihexyphenidyl | PO | Dystonia (focal or generalized) | 1 mg :: PO :: daily :: Start 1 mg daily; increase by 1 mg every 3-5 days; target 6-15 mg/day divided TID; max 15 mg/day | Glaucoma, urinary retention, dementia, age >65 | Confusion, dry mouth, urinary retention, cognitive impairment | - | ROUTINE | ROUTINE | - |
| Levodopa/Carbidopa | PO | Parkinsonism (rigidity, bradykinesia) | 100 mg :: PO :: TID :: Start 25/100 mg TID; titrate by 25/100 mg q1-2 weeks; limited efficacy in WD parkinsonism (response variable) | Narrow-angle glaucoma | Dyskinesia, nausea, orthostatic hypotension; often poor response in WD | - | ROUTINE | ROUTINE | - |
| Clonazepam | PO | Tremor, dystonia, chorea, sleep disturbance | 0.5 mg :: PO :: BID :: Start 0.5 mg BID; titrate by 0.5 mg q3-5 days; max 4 mg/day | Respiratory depression, severe hepatic disease, addiction risk | Sedation, respiratory depression, dependence; adjust dose in hepatic impairment | - | ROUTINE | ROUTINE | ROUTINE |
| Botulinum toxin (OnabotulinumtoxinA) | IM | Focal dystonia (cervical, oromandibular, limb) | Dose per target :: IM :: q3 months :: Site-specific dosing: cervical dystonia 100-300 units; limb dystonia 50-200 units per muscle; q12 weeks | Infection at injection site, myasthenia gravis | Weakness at injection site, dysphagia (cervical injections) | - | - | ROUTINE | - |
| Propranolol | PO | Tremor (postural/action component) | 20 mg :: PO :: BID :: Start 20 mg BID; titrate to 120-240 mg/day; limited efficacy for wing-beating tremor | Asthma, COPD, bradycardia, decompensated heart failure | HR, BP | - | ROUTINE | ROUTINE | - |
| Sertraline | PO | Depression, anxiety (common in WD) | 25 mg :: PO :: daily :: Start 25 mg daily; titrate to 100-200 mg/day | MAOI use; caution with hepatic impairment (reduce dose) | Hepatic function (use lower doses in liver disease); suicidality in young adults | - | ROUTINE | ROUTINE | - |
| Quetiapine | PO | Psychosis, agitation, behavioral disturbance | 12.5 mg :: PO :: QHS :: Start 12.5 mg QHS; titrate cautiously to 50-200 mg/day; avoid typical antipsychotics (worsen movement disorder) | QTc prolongation; avoid typical antipsychotics (D2 blockade worsens dystonia/parkinsonism) | QTc, metabolic panel, sedation; use ONLY atypical antipsychotics | - | ROUTINE | ROUTINE | ROUTINE |
| Gabapentin | PO | Neuropathic pain, tremor (adjunctive) | 300 mg :: PO :: TID :: Start 300 mg QHS; increase by 300 mg/day every 3 days; target 900-1800 mg/day TID | Severe renal impairment (dose adjust) | Sedation, dizziness | - | ROUTINE | ROUTINE | - |
| Omeprazole | PO | GI protection during chelation therapy | 20 mg :: PO :: daily :: 20 mg PO daily; take 30 min before chelator | None absolute | Long-term: B12, Mg levels | - | ROUTINE | ROUTINE | - |
3C. Second-line/Refractory¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Liver transplantation evaluation | Referral | Fulminant hepatic failure; decompensated cirrhosis unresponsive to chelation; severe neurologic WD refractory to 6+ months chelation (controversial) | Refer to transplant center :: - :: - :: Urgent evaluation in fulminant WD (New Wilson Index ≥11 = transplant); King's Wilson criteria; MELD score >15 or acute liver failure | Absolute contraindications per transplant center protocol | Pre-transplant workup; transplant corrects metabolic defect (no lifelong chelation needed post-transplant) | - | URGENT | ROUTINE | STAT |
| Continuous venovenous hemofiltration (CVVH) | Extracorporeal | Fulminant WD with renal failure or massive hemolysis; bridge to transplant | Per ICU protocol :: Extracorporeal :: continuous :: Continuous copper removal; bridge therapy to transplant | N/A (life-saving in ICU) | Copper levels, hemodynamics, electrolytes | - | - | - | STAT |
| Molecular adsorbent recirculating system (MARS) | Extracorporeal | Fulminant WD; albumin dialysis removes copper | Per protocol :: Extracorporeal :: per session :: Albumin dialysis; available at specialized centers; bridge to transplant | Hemodynamic instability | Copper levels, bilirubin, coagulation, hemodynamics | - | EXT | - | EXT |
| Tetrathiomolybdate (ammonium or bis-choline) | PO | Investigational chelator; neurologic WD (may have less neurologic worsening than penicillamine) | 20 mg :: PO :: TID :: 20 mg TID with meals + 20 mg TID between meals (total 120 mg/day); investigational — available through clinical trials or compassionate use | Severe hepatic failure; not yet widely approved | CBC (bone marrow suppression), LFTs, copper levels, iron studies (iron deficiency from over-decoppering) | - | EXT | EXT | - |
3D. Disease-Modifying Therapies (Chelation & Zinc)¶
| Treatment | Route | Indication | Dosing | Pre-Treatment Requirements | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|---|
| D-Penicillamine (Cuprimine) | PO | First-line chelation (symptomatic WD — hepatic or neurologic); removes copper via renal excretion | 250 mg :: PO :: daily :: Start 250-500 mg/day; increase by 250 mg every 4-7 days; target 1000-1500 mg/day divided BID-QID; take on empty stomach (1h before or 2h after meals); SLOW titration reduces neurologic worsening risk | Baseline: CBC, UA, CMP, 24h urine copper; pyridoxine 25 mg/day (penicillamine depletes B6); pregnancy test in women of childbearing age | Penicillin allergy (may cross-react); pregnancy (teratogenic — switch to zinc); lupus-like syndrome; prior severe adverse reaction | CBC weekly x1 month then monthly x6 months then q3 months; UA for proteinuria every 2 weeks x3 months then monthly; LFTs monthly; 24h urine copper q3-6 months (target 200-500 mcg/24h on treatment); watch for neurologic WORSENING in first 6-8 weeks (occurs in 10-50%) | - | STAT | ROUTINE | STAT |
| Trientine (Syprine, TETA) | PO | Alternative first-line chelator; preferred if penicillamine intolerant or neurologic presentation (lower risk of neurologic worsening); removes copper via renal excretion | 250 mg :: PO :: BID :: Start 500-750 mg/day divided BID-TID; target 750-1500 mg/day; take on empty stomach (1h before or 2h after meals); available as trientine dihydrochloride or trientine tetrahydrochloride (Cuvrior — different dosing) | Baseline: CBC, CMP, 24h urine copper; iron studies (trientine chelates iron); pregnancy test | Pregnancy (teratogenic — switch to zinc); iron deficiency anemia (monitor closely) | CBC monthly x6 months then q3 months; LFTs monthly x6 months then q3 months; 24h urine copper q3-6 months (target 200-500 mcg/24h); iron studies q6 months (sideropenia risk); watch for neurologic worsening (less common than penicillamine, ~10-15%) | - | STAT | ROUTINE | STAT |
| Zinc acetate (Galzin) | PO | Maintenance therapy (after initial decoppering with chelator); mild/presymptomatic WD; pregnancy (safest option); family members with pre-clinical WD | 50 mg :: PO :: TID :: 50 mg elemental zinc TID (taken as zinc acetate 150 mg TID); take on empty stomach separated from meals by ≥1 hour; separate from chelator by ≥2 hours if used concurrently | Baseline: CBC, CMP, 24h urine copper, serum zinc level | None absolute; GI intolerance common (nausea); do NOT use as sole therapy in symptomatic/severe WD (too slow onset) | 24h urine copper q3-6 months (target <75 mcg/24h on zinc monotherapy); serum zinc level q3-6 months (target 125-150 mcg/dL); 24h urine zinc (confirms compliance: >2 mg/24h); LFTs q3-6 months; CBC q6 months (zinc-induced copper deficiency can cause neutropenia) | - | ROUTINE | ROUTINE | - |
| Zinc sulfate (alternative zinc formulation) | PO | Alternative to zinc acetate for maintenance therapy; more GI side effects but less expensive | 220 mg :: PO :: TID :: 220 mg zinc sulfate TID (contains ~50 mg elemental zinc per 220 mg); take on empty stomach separated from meals by ≥1 hour; separate from chelator by ≥2 hours if used concurrently | Baseline: CBC, CMP, 24h urine copper, serum zinc level | GI intolerance common (nausea, gastric irritation); do NOT use as sole therapy in symptomatic/severe WD (too slow onset) | 24h urine copper q3-6 months (target <75 mcg/24h on zinc monotherapy); serum zinc level q3-6 months (target 125-150 mcg/dL); 24h urine zinc (confirms compliance: >2 mg/24h); LFTs q3-6 months; CBC q6 months (zinc-induced copper deficiency can cause neutropenia) | - | ROUTINE | ROUTINE | - |
| Pyridoxine (Vitamin B6) | PO | Required supplement with D-penicillamine therapy (penicillamine depletes B6) | 25 mg :: PO :: daily :: 25 mg PO daily; co-administer with penicillamine | None | None | Clinical assessment; peripheral neuropathy symptoms | - | ROUTINE | ROUTINE | - |
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU | Indication |
|---|---|---|---|---|---|
| Hepatology consultation | STAT | STAT | ROUTINE | STAT | All WD patients; liver disease staging, transplant evaluation, chelation management |
| Neurology consultation | URGENT | STAT | ROUTINE | STAT | All neurologic WD; movement disorder management, monitoring for chelation-related worsening |
| Movement disorder specialist | - | ROUTINE | ROUTINE | - | Dystonia, tremor, parkinsonism management; botulinum toxin injections |
| Ophthalmology (slit-lamp exam) | URGENT | STAT | ROUTINE | - | ALL suspected WD — Kayser-Fleischer ring assessment; sunflower cataract screening |
| Genetics / Genetic counselor | - | ROUTINE | ROUTINE | - | ATP7B testing confirmation, family screening, reproductive counseling |
| Transplant hepatology/surgery | - | STAT | ROUTINE | STAT | Fulminant hepatic failure, decompensated cirrhosis, New Wilson Index ≥11 |
| Psychiatry | - | ROUTINE | ROUTINE | - | Depression, psychosis, personality change, behavioral disturbance (common in WD) |
| Neuropsychology | - | - | ROUTINE | - | Baseline cognitive assessment; monitor for cognitive decline |
| Speech-language pathology (SLP) | - | ROUTINE | ROUTINE | - | Dysarthria, dysphagia evaluation and management |
| Physical therapy (PT) | - | ROUTINE | ROUTINE | - | Dystonia management, gait training, falls prevention |
| Occupational therapy (OT) | - | ROUTINE | ROUTINE | - | ADL assistance, handwriting aids, adaptive equipment |
| Nutrition / Dietitian | - | ROUTINE | ROUTINE | - | Low-copper diet counseling; hepatic diet if cirrhotic |
| Social work | - | ROUTINE | ROUTINE | - | Chronic disease support, medication access (chelators are expensive), disability resources |
4B. Patient/Family Instructions¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Wilson's disease is a lifelong condition requiring CONTINUOUS treatment — never stop chelation or zinc without physician guidance | - | STAT | ROUTINE | - |
| Take chelation medication (penicillamine or trientine) on an EMPTY STOMACH — 1 hour before or 2 hours after meals | - | ROUTINE | ROUTINE | - |
| If taking zinc, separate from chelator by at least 2 hours; take zinc between meals | - | ROUTINE | ROUTINE | - |
| Return to ED if: worsening jaundice, confusion, vomiting blood, black stools, new neurologic symptoms, worsening speech or swallowing, severe abdominal pain | STAT | ROUTINE | ROUTINE | - |
| Report ANY new neurologic symptoms during the first 2-3 months of chelation (worsening is possible and requires dose adjustment) | - | STAT | ROUTINE | - |
| Avoid HIGH-COPPER FOODS during initial treatment: liver/organ meats, shellfish (especially lobster, oysters), chocolate, mushrooms, nuts, dried fruits, soy products | - | ROUTINE | ROUTINE | - |
| Avoid drinking water through copper pipes (consider water testing; use filter or bottled water if copper pipes present) | - | ROUTINE | ROUTINE | - |
| Alcohol is STRICTLY prohibited — causes additional liver damage | - | ROUTINE | ROUTINE | - |
| Women of childbearing age: pregnancy requires switching from chelator to zinc (chelators are teratogenic); discuss family planning with physician BEFORE conception | - | ROUTINE | ROUTINE | - |
| ALL first-degree relatives (siblings, children, parents) MUST be screened for Wilson's disease — siblings have 25% risk | - | ROUTINE | ROUTINE | - |
| Carry a medical alert card/bracelet indicating Wilson's disease and current medications | - | ROUTINE | ROUTINE | - |
| Regular follow-up is ESSENTIAL — blood and urine tests needed every 3-6 months lifelong | - | ROUTINE | ROUTINE | - |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Low-copper diet during initial decoppering phase (avoid >1 mg copper/day); can liberalize slightly once stable on treatment | - | ROUTINE | ROUTINE | - |
| Regular exercise as tolerated; may improve dystonia and mood | - | ROUTINE | ROUTINE | - |
| Strict alcohol avoidance (lifelong — hepatotoxic) | - | ROUTINE | ROUTINE | - |
| Smoking cessation (impairs liver function and overall health) | - | ROUTINE | ROUTINE | - |
| Hepatitis A and B vaccination if not immune (protect remaining liver function) | - | ROUTINE | ROUTINE | - |
| Avoid hepatotoxic medications (acetaminophen limit <2 g/day; avoid NSAIDs if cirrhotic; avoid statins if decompensated) | - | ROUTINE | ROUTINE | - |
| Genetic counseling for reproductive planning; autosomal recessive — both parents are carriers; 25% risk for each sibling | - | - | ROUTINE | - |
| Mental health support; depression and anxiety are common and treatable components of WD | - | ROUTINE | ROUTINE | - |
| Screen all first-degree relatives: ceruloplasmin, 24h urine copper, LFTs, slit-lamp exam, ATP7B genetic testing | - | - | ROUTINE | - |
═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Autoimmune hepatitis | Young women, positive ANA/SMA/anti-LKM, elevated IgG, no KF rings, no neurologic features; can coexist with WD | ANA, SMA, IgG level, liver biopsy; ceruloplasmin, copper studies |
| Drug-induced parkinsonism | Temporal relationship to dopamine-blocking medication, symmetric, resolves with drug withdrawal | Medication review; ceruloplasmin normal; no KF rings |
| Idiopathic Parkinson's disease | Asymmetric onset, rest tremor (pill-rolling), levodopa-responsive, age >50 typically, no hepatic involvement | DaTscan; ceruloplasmin, 24h urine copper; slit-lamp (no KF rings) |
| Juvenile Huntington's disease | Family history (AD), progressive chorea, behavioral changes, caudate atrophy on MRI | Genetic testing (HTT CAG repeat); ceruloplasmin normal |
| Dystonia (primary/DYT) | Isolated dystonia without hepatic features, family history, onset typically in limb, no KF rings | Genetic testing (DYT1, etc.); ceruloplasmin normal; no hepatic involvement |
| Hemochromatosis | Iron overload, skin bronzing, diabetes, arthropathy, hepatic disease, no neurologic copper features | Iron studies (elevated ferritin, transferrin saturation); HFE gene; ceruloplasmin normal |
| Non-alcoholic fatty liver disease (NAFLD) | Metabolic syndrome, obesity, insulin resistance, no neurologic features, no KF rings | Metabolic workup; ceruloplasmin normal; liver biopsy (steatosis without copper) |
| Viral hepatitis (B, C) | Exposure risk factors, positive viral serologies, no KF rings or neurologic features | Hepatitis panel; ceruloplasmin normal |
| Alcoholic liver disease | Alcohol use history, AST:ALT ratio >2, no KF rings, no neurologic copper features | History; ceruloplasmin normal; liver biopsy |
| Neuroacanthocytosis | Orofacial dyskinesia, chorea, self-mutilation, acanthocytes on blood smear | Peripheral smear (acanthocytes); CK (elevated); ceruloplasmin normal |
| Menkes disease | X-linked; presents in infancy (not adolescent/adult); kinky hair, seizures, failure to thrive | Age of onset; genetic testing (ATP7A); ceruloplasmin very low but different gene |
| Pantothenate kinase-associated neurodegeneration (PKAN) | "Eye of the tiger" sign on MRI (globus pallidus), dystonia, retinopathy | MRI (iron deposition pattern differs from WD); PANK2 gene |
| Acquired hepatocerebral degeneration | Chronic liver disease from ANY cause; parkinsonism, ataxia; MRI shows T1 basal ganglia signal (manganese) | Underlying liver disease diagnosis; ceruloplasmin may be low from liver failure but 24h urine copper not markedly elevated; no ATP7B mutations |
| Multiple sclerosis | Relapsing white matter disease, optic neuritis, spinal cord lesions; no hepatic involvement | MRI brain/spine (demyelination); LP (oligoclonal bands); ceruloplasmin normal |
6. MONITORING PARAMETERS¶
| Parameter | ED | HOSP | OPD | ICU | Frequency | Target/Threshold | Action if Abnormal |
|---|---|---|---|---|---|---|---|
| 24-hour urine copper | - | STAT | ROUTINE | STAT | q3-6 months on chelation; q6-12 months on zinc maintenance | Chelation target: 200-500 mcg/24h; Zinc target: <75 mcg/24h | Adjust chelator dose if outside range; <200 suggests over-chelation or non-compliance |
| Serum free (non-ceruloplasmin-bound) copper | - | STAT | ROUTINE | STAT | q3-6 months | <15 mcg/dL on treatment; negative values suggest over-treatment | Reduce chelator if over-treated; increase if still elevated |
| LFTs (AST, ALT, bilirubin, albumin) | STAT | STAT | ROUTINE | STAT | Monthly x6 months, then q3-6 months | Normalizing or stable | If worsening on treatment: assess compliance, consider dose adjustment, transplant evaluation |
| CBC with differential | STAT | STAT | ROUTINE | STAT | Weekly x1 month (penicillamine), then monthly x6 months, then q3 months | WBC >3000, platelets >100K, Hgb stable | Penicillamine: hold if WBC <3000 or platelets <100K (bone marrow suppression); neutropenia on zinc (copper deficiency) |
| INR/PT | STAT | STAT | ROUTINE | STAT | Monthly x6 months, then q3-6 months | Normalizing (<1.3) | Worsening INR suggests progressive liver disease; transplant evaluation if persistent |
| Urinalysis (for proteinuria) | - | ROUTINE | ROUTINE | - | Every 2 weeks x3 months on penicillamine, then monthly | No proteinuria (>1+ protein warrants investigation) | Penicillamine nephrotoxicity: hold if >1 g/24h proteinuria; may require switch to trientine |
| Serum zinc level | - | ROUTINE | ROUTINE | - | q3-6 months on zinc therapy | 125-150 mcg/dL (therapeutic range) | Low: assess compliance; High: reduce dose |
| 24-hour urine zinc | - | - | ROUTINE | - | q6-12 months | >2 mg/24h confirms compliance | Low suggests non-compliance |
| Neurologic exam (dystonia, tremor, speech, gait) | URGENT | STAT | ROUTINE | STAT | Each visit; monthly during initial chelation | Stable or improving; no new deficits | If WORSENING in first 2-3 months: reduce chelator dose, consider switch to trientine or add zinc; persistent worsening → transplant evaluation |
| Slit-lamp exam (KF rings) | - | STAT | ROUTINE | - | Annually on treatment | Gradual fading of KF rings (may take 3-5 years) | Persistence or reappearance suggests inadequate treatment or non-compliance |
| MRI brain | - | ROUTINE | ROUTINE | - | Baseline; repeat at 6-12 months; then annually x3 years if neurologic | Improving or stable signal abnormalities; resolving edema | Worsening lesions suggest inadequate treatment or chelation-induced worsening |
| Hepatic fibrosis assessment (FibroScan or biomarkers) | - | - | ROUTINE | - | Annually if cirrhotic | Stable or improving stiffness | Worsening fibrosis despite treatment: re-evaluate; transplant referral |
| Iron studies | - | ROUTINE | ROUTINE | - | q6 months on trientine | Normal ferritin and iron | Trientine chelates iron → sideropenia; supplement iron if deficient (separate from trientine by 2h) |
| Bone density (DEXA) | - | - | ROUTINE | - | Baseline; repeat q2 years | T-score > -2.5 | Treat osteoporosis; calcium/vitamin D supplementation |
| Depression/psychiatric screening | - | ROUTINE | ROUTINE | - | Each visit | Stable mood, no psychosis | Psychiatric referral; adjust medications |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| Discharge home | Diagnosis established; chelation/zinc initiated and tolerated; stable neurologic exam; no hepatic decompensation; able to take oral medications; understands dietary restrictions and medication timing; follow-up arranged within 1-2 weeks |
| Admit to floor | New diagnosis requiring inpatient workup; initiation of chelation therapy with monitoring; hepatic decompensation (ascites, jaundice, coagulopathy); moderate neurologic symptoms requiring inpatient management; inability to take oral medications |
| Admit to ICU | Fulminant hepatic failure (encephalopathy, coagulopathy, renal failure); severe hemolytic crisis; status epilepticus; severe dystonic crisis with airway compromise; pending liver transplant evaluation |
| Transfer to liver transplant center | Fulminant Wilson's disease (New Wilson Index ≥11); decompensated cirrhosis unresponsive to chelation; King's criteria met; MELD score >15 with progressive decline |
| Outpatient management | Stable on chelation or zinc maintenance; routine monitoring labs; presymptomatic WD diagnosed through family screening; mild hepatic or neurologic disease responding to treatment |
| Inpatient rehabilitation | Severe dystonia or parkinsonism affecting function; dysphagia requiring supervised feeding; gait instability requiring intensive PT |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| Ceruloplasmin <20 mg/dL as screening test for WD | Class II, Level B | Ferenci et al., Liver Int 2003 PubMed: 14506258 |
| 24-hour urine copper >100 mcg as diagnostic criterion | Class II, Level B | Roberts & Schilsky, Hepatology 2008 (AASLD Practice Guidelines) PubMed: 18506894 |
| D-Penicillamine as first-line chelation therapy | Class II, Level B | Walshe, Lancet 1956; Roberts & Schilsky, Hepatology 2008 PubMed: 18506894 |
| Trientine as alternative first-line chelator with lower neurologic worsening risk | Class II, Level B | Walshe, Lancet 1982; Weiss et al., J Hepatol 2013 PubMed: 23485523 |
| Zinc acetate for maintenance therapy | Class II, Level B | Brewer et al., Arch Neurol 1987; Czlonkowska et al., Ann Neurol 1996 PubMed: 8967753 |
| Neurologic worsening occurs in 10-50% of patients starting D-penicillamine | Class II, Level B | Brewer et al., Arch Neurol 1994 PubMed: 7944997; Walshe & Yealland, J Neurol Neurosurg Psychiatry 1993 PubMed: 8505642 |
| Liver transplantation for fulminant WD and decompensated cirrhosis | Class I, Level B | Arnon et al., Hepatology 2011 PubMed: 21254169; Dhawan et al., Gut 2005 PubMed: 15753547 |
| New Wilson Index ≥11 predicts need for transplantation in pediatric fulminant WD | Class II, Level B | Dhawan et al., Gut 2005 PubMed: 15753547 |
| Kayser-Fleischer rings present in >95% of neurologic WD | Class II, Level B | Walshe, Brain 1976; Ala et al., Lancet 2007 PubMed: 17276780 |
| Leipzig Scoring System for WD diagnosis (score ≥4 = established) | Class IIa, Level C | Ferenci et al., Liver Int 2003 (8th International Meeting on Wilson Disease) PubMed: 14506258 |
| ATP7B gene testing for definitive diagnosis and family screening | Class I, Level B | Loudianos & Gitlin, Semin Liver Dis 2000 PubMed: 11200483; EASL Clinical Practice Guidelines 2012 PubMed: 22276820 |
| MRI brain findings: T2 hyperintensity in putamen ("face of giant panda" sign) | Class II, Level C | King et al., Mov Disord 1996 PubMed: 8866494; Sinha et al., AJNR 2006 PubMed: 16551993 |
| Low-copper diet during initial decoppering phase | Class III, Level C | Expert consensus; EASL Clinical Practice Guidelines 2012 PubMed: 22276820 |
| Plasmapheresis for acute hemolytic crisis in fulminant WD | Class IIb, Level C | Jhang et al., J Clin Apher 2007 PubMed: 17722038; Akyildiz et al., Ther Apher Dial 2004 PubMed: 15255163 |
| Free (non-ceruloplasmin-bound) copper as monitoring parameter | Class II, Level B | Walshe, Ann Clin Biochem 2003 PubMed: 12880538; EASL Clinical Practice Guidelines 2012 PubMed: 22276820 |
| Pregnancy management: switch to zinc; chelators are teratogenic | Class II, Level C | Brewer et al., J Lab Clin Med 2000 PubMed: 10638697; Tarnacka et al., Fertil Steril 2000 PubMed: 10685533 |
| Family screening with ceruloplasmin, 24h urine copper, and ATP7B genotyping | Class I, Level B | EASL Clinical Practice Guidelines 2012 PubMed: 22276820; Roberts & Schilsky, Hepatology 2008 PubMed: 18506894 |
| AASLD Practice Guidelines for Wilson Disease | Class I (Guidelines) | Roberts & Schilsky, Hepatology 2008 PubMed: 18506894; Schilsky, Clin Liver Dis 2017 PubMed: 28364808 |
| EASL Clinical Practice Guidelines on Wilson's Disease | Class I (Guidelines) | European Association for the Study of the Liver, J Hepatol 2012 PubMed: 22276820 |
| Trientine tetrahydrochloride (Cuvrior) as improved formulation | Class II, Level B | Weiss et al., Lancet Gastroenterol Hepatol 2022 PubMed: 35276119 |
| Bis-choline tetrathiomolybdate for neurologic WD (phase 3 data) | Class II, Level B | Weiss et al., Lancet Gastroenterol Hepatol 2022 (WTX101-301 trial) PubMed: 35276119 |
NOTES¶
- Wilson's disease is a TREATABLE cause of liver failure and neurologic decline — early diagnosis is critical
- Consider WD in ANY patient <50 years with unexplained liver disease, movement disorder, or psychiatric illness
- Ceruloplasmin alone misses 5-15% of cases; always obtain 24-hour urine copper and slit-lamp exam
- The Leipzig Score integrates multiple tests for diagnostic certainty (score ≥4 = WD established)
- D-penicillamine is effective but causes neurologic WORSENING in 10-50% of patients during initial weeks; many experts now prefer trientine as first-line for neurologic WD
- Zinc monotherapy is too slow for symptomatic disease but is ideal for maintenance and presymptomatic patients
- NEVER stop chelation/zinc abruptly — can precipitate fulminant hepatic failure or neurologic crisis
- Avoid typical antipsychotics (haloperidol, etc.) — D2 blockade worsens dystonia and parkinsonism; use quetiapine or clozapine if antipsychotic needed
- Fulminant Wilson's disease: Coombs-negative hemolytic anemia + acute liver failure + low ALP + low ALP-to-bilirubin ratio is classic triad; requires urgent transplant evaluation
- All first-degree relatives MUST be screened; siblings have 25% risk of being affected
- Liver transplantation CURES the metabolic defect — post-transplant patients do not need chelation
- MRI brain may lag behind clinical improvement by months; initial worsening of MRI does not necessarily indicate treatment failure
- When using combined chelation + zinc therapy, separate zinc from chelator by ≥2 hours (zinc blocks chelator absorption if given together); some experts use chelator + zinc simultaneously for initial treatment of symptomatic WD
CHANGE LOG¶
v1.1 (January 30, 2026) - Fixed ICD-10 codes: removed K74.3 (primary biliary cirrhosis — not a WD code) and G25.0 (essential tremor — not appropriate for WD tremor); added G25.2 (other specified forms of tremor) per C3, C4 - Removed "Combined chelation + zinc" row from Section 3D (used cross-references "Per individual agents"); moved combination note to NOTES section per C1, R1 - Made Zinc sulfate row fully self-contained: expanded Pre-Treatment, Contraindications, and Monitoring fields (previously "Same as zinc acetate") per C2, R2 - Updated Pyridoxine Monitoring from "None specific" to "Clinical assessment; peripheral neuropathy symptoms" and Contraindications from "None specific" to "None" per M5 - Standardized starting doses: Propranolol (20 mg), Sertraline (25 mg), Quetiapine (12.5 mg) — changed from ranges per R5, M2-M4 - Updated Plasmapheresis Route to "Extracorporeal" (was "-") per S1, R9 - Updated CVVH Route to "Extracorporeal" (was "IV") and MARS Route to "Extracorporeal" (was "-") per S2 - Updated Liver transplantation evaluation Route to "Referral" (was "-") per S2 - Added ICU column to Section 4B (Patient/Family Instructions) and Section 4C (Lifestyle & Prevention) tables per S3, S4 - Added Chest X-ray to Section 2A (Essential imaging) for ICU/fulminant hepatic failure patients per R6 - Added PubMed citation links to all 22 references in Section 8 per R7 - Added REVISED date to header metadata - Version bump from 1.0 to 1.1
v1.0 (January 30, 2026) - Initial template creation - Comprehensive diagnostic workup including Leipzig Score components - Chelation therapy with structured dosing (D-penicillamine, trientine, zinc) - Symptomatic management for dystonia, tremor, parkinsonism, psychiatric symptoms - Fulminant hepatic failure acute management - Liver transplant evaluation criteria - Family screening recommendations - 22 evidence-based references with author, journal, and year