Wilson Disease: Clinical Case Discussion & Key Points
Model Case Presentation
Patient Demographics
Name: Master Arjun, Age: 11 years, Gender: Male, Informant: Mother (Reliable)
Chief Complaints
- Jaundice – 3 months
- Abdominal distension – 2 months
- Declining school performance and behavioral changes – 6 months
History Summary
An 11-year-old boy presents with insidious onset jaundice over 3 months, associated with abdominal distension (ascites), anorexia, and easy fatigability. Mother reports the child has become irritable, forgetful, and his handwriting has deteriorated over the past 6 months. He has had two prior hospitalizations for "hepatitis" — once at age 8 and once at age 10 — with partial recovery each time. He also had an episode of passing dark urine during the first hospitalization (hemolytic crisis). No history of blood transfusion, jaundiced contacts, alcohol, or hepatotoxic drug use. Parents are first-degree cousins (consanguineous marriage). Maternal uncle reportedly had "liver disease" of unknown etiology and died in early adulthood.
Born at term via NVD. Developmental milestones normal until about age 9, after which school performance began to decline.
Examination Summary
| Parameter | Finding | Significance |
|---|---|---|
| Jaundice | Present (scleral icterus) | Hepatic/hemolytic |
| Kayser-Fleischer Rings | Present (slit-lamp) | Hallmark of Wilson disease |
| Liver | 4 cm below RCM, firm, non-tender | Hepatomegaly (cirrhosis) |
| Spleen | 3 cm below LCM | Portal hypertension |
| Abdomen | Shifting dullness +ve | Ascites |
| Tremor | Wing-beating tremor at rest | Basal ganglia involvement |
| Speech | Dysarthria | Neurological Wilson |
| Pallor | Present | Hemolytic anemia |
| Cyanosis/Clubbing | Absent | — |
Neurological: Dysarthria, coarse "wing-beating" tremor when arms extended at shoulder level. No frank dystonia. Cognitive assessment: inattentive, poor recall.
Skin: No spider nevi or palmar erythema at this age; mild icterus.
Eyes: Kayser-Fleischer (KF) rings confirmed on slit-lamp examination — golden-brown rings at the periphery of the cornea in Descemet's membrane.
✅ Complete Diagnosis
Wilson Disease (Hepatolenticular Degeneration) — Mixed Hepatic and Neurological Presentation with Cirrhosis, Portal Hypertension, Ascites, Hemolytic Anemia, and Neuropsychiatric Involvement (Dysarthria, Wing-Beating Tremor). KF rings present. Likely Leipzig Score ≥ 4.
📝 History — Exam Q&A
Wilson disease (WD), also called Hepatolenticular Degeneration, is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene on chromosome 13q14.3.
The ATP7B gene encodes a copper-transporting P-type ATPase in hepatocytes. Dysfunction leads to:
- Failure of copper excretion into bile (main route of copper elimination)
- Defective incorporation of copper into ceruloplasmin
- Copper accumulation in liver → brain → cornea → kidneys → other organs
Prevalence: ~1 in 30,000. Over 500 mutations identified in ATP7B.
Wilson disease typically presents between 5–35 years of age. Rarely presents before age 5 (copper still accumulating).
- Children (5–12 years): Predominantly hepatic presentation
- Adolescents/Young adults (12–35 years): Neuropsychiatric presentation becomes more prominent
- Hepatic disease always precedes neurological disease (liver is the first organ affected)
💡 Key Point
WD should always be considered in any child >5 years with unexplained liver disease, unexplained hemolytic anemia, or behavioral/school deterioration.
Hepatic disease is the most common presentation in children (~85%). Presentations include:
| Mode | Features |
|---|---|
| Asymptomatic | Incidentally elevated LFTs or discovered on family screening |
| Acute Hepatitis | Jaundice, fatigue, nausea; often self-limiting; may be misdiagnosed as viral hepatitis |
| Recurrent Hepatitis | Repeated episodes; characteristic of WD in children |
| Chronic Hepatitis / Cirrhosis | Insidious progression; hepatomegaly, splenomegaly, portal hypertension, ascites |
| Acute Liver Failure (ALF) | Dramatic; associated with Coombs-negative hemolytic anemia (pathognomonic combination) |
Neurological (due to copper in basal ganglia/brain stem):
- Tremor: Wing-beating (asterixis-like) tremor — arms extended at shoulder, flap rhythmically; or intention tremor
- Dysarthria: Slurred, scanning speech
- Dysphagia
- Dystonia: Sustained abnormal postures
- Parkinsonism: Bradykinesia, rigidity, mask-like facies
- Ataxia, drooling, gait abnormalities
Psychiatric (often the first symptom, easily missed):
- Behavioral changes, irritability
- Personality changes, depression, anxiety
- Cognitive decline, poor school performance
- Psychosis (rare)
🚨 Exam Tip
Neurological symptoms rarely occur before age 10 in children. Psychiatric symptoms often precede frank neurological findings by months to years and may be misdiagnosed as primary psychiatric disorders.
Acute release of large amounts of copper from damaged liver cells causes direct oxidative damage to red blood cells → intravascular hemolysis.
- Hemolysis is Coombs (DAT) negative — distinguishes it from autoimmune hemolytic anemia
- It is non-immune mediated (copper-induced RBC membrane damage)
- Associated with: dark urine, pallor, jaundice worsening
- The combination of acute liver failure + Coombs-negative hemolytic anemia is virtually pathognomonic of Wilson disease and warrants urgent evaluation
Normal copper metabolism: Dietary copper → absorbed in small intestine → transported to liver → ATP7B pumps copper into bile (main excretion) and incorporates it into ceruloplasmin.
In Wilson disease:
- ATP7B is dysfunctional → copper cannot be exported into bile
- Copper accumulates in hepatocytes → hepatocyte death → copper spills into circulation
- Free (non-ceruloplasmin-bound) copper deposits in: brain (lenticular nucleus = putamen + globus pallidus), cornea (KF rings), kidneys, heart, bones, joints
- Ceruloplasmin synthesis is defective → low serum ceruloplasmin
| System | Manifestation |
|---|---|
| Renal | Fanconi syndrome (proximal tubular dysfunction) → aminoaciduria, glycosuria (without hyperglycemia), phosphaturia, uricosuria, hematuria; renal tubular acidosis |
| Skeletal | Osteoporosis, osteomalacia, arthropathy, premature osteoarthritis |
| Hematological | Coombs-negative hemolytic anemia, thrombocytopenia (hypersplenism), leukopenia |
| Cardiac | Cardiomyopathy, arrhythmias (rare) |
| Endocrine | Hypoparathyroidism, amenorrhea, infertility, delayed puberty |
| Eyes | KF rings (cornea), Sunflower cataract (lens — copper deposits) |
| Skin | Azure lunulae (blue discoloration of nail lunulae — rare) |
Pertinent Positives:
- Recurrent hepatitis episodes (partial recovery each time)
- Dark urine during hepatitis episodes (hemolysis)
- Behavioral changes, declining school performance (neuropsychiatric)
- Tremor, speech changes, clumsiness (neurological)
- Consanguineous marriage in parents (autosomal recessive)
- Family history of unexplained liver disease or early death
Pertinent Negatives:
- No history of blood transfusion (rules out transfusion-related hepatitis/hemolysis)
- No history of jaundiced contacts (rules out viral hepatitis)
- No hepatotoxic drug use
- No alcohol use
- Coombs test negative (rules out autoimmune hemolysis)
🩺 Examination — Exam Q&A
Kayser-Fleischer (KF) rings are golden-brown to greenish rings at the periphery of the cornea, representing copper deposits in Descemet's membrane (deep layer of cornea).
- Detection: Slit-lamp examination by an ophthalmologist — mandatory for confirmation. Visible to naked eye only in advanced cases.
- Location: Start superiorly and inferiorly, then complete the ring circumferentially
- Significance: Present in ~95–100% of neurological WD and ~50–60% of hepatic WD in children (less frequent in young children)
🚨 Important
KF rings are NOT specific for WD — they also occur in chronic cholestatic liver diseases (PBC, PSC, biliary atresia). However, in the context of liver disease + neurological symptoms, KF rings are highly significant for WD.
Wing-beating tremor (also called "asterixis-like" or "bat-wing tremor") is a coarse, proximal tremor involving the shoulder girdle.
How to elicit: Ask the patient to extend both arms laterally at shoulder level with elbows bent (like a bird spreading wings) — the arms flap rhythmically, resembling a bird beating its wings.
Pathophysiology: Due to copper deposition in the putamen and globus pallidus (lenticular nucleus) causing disruption of extrapyramidal circuits.
Note: Wilson disease also causes intention tremor (cerebellar), postural tremor, and rest tremor (parkinsonism-like) — the wing-beating type is most characteristic.
Liver disease signs:
- Jaundice, scleral icterus
- Hepatomegaly (firm, smooth edge in cirrhosis)
- Spider nevi, palmar erythema (chronic liver disease — less prominent in children)
- Leukonychia, parotid enlargement
Portal hypertension signs:
- Splenomegaly (most common sign)
- Ascites (shifting dullness, fluid thrill)
- Caput medusae (dilated abdominal veins)
- Dilated veins on chest wall
Note: In WD with cirrhosis, the liver may actually be small and shrunken in late stages.
A sunflower (chalcosis lentis) cataract is a disc-shaped, greenish-brown opacity in the anterior capsule of the lens with petal-like radiations — resembling a sunflower.
- Due to copper deposition in the lens
- Detected on slit-lamp examination
- Seen in ~20% of WD patients
- Does not usually cause visual impairment
- Regresses with copper chelation therapy
| Sign | Implication |
|---|---|
| Wing-beating / intention / postural tremor | Basal ganglia / cerebellar involvement |
| Dysarthria (scanning/slurred speech) | Cerebellar + corticobulbar dysfunction |
| Dysphagia | Pseudobulbar involvement |
| Dystonia (abnormal sustained postures) | Basal ganglia |
| Rigidity, bradykinesia | Parkinsonism-like (putamen involvement) |
| Gait ataxia | Cerebellar involvement |
| Drooling | Facial muscle involvement |
| Mask-like facies | Parkinsonism |
Cognitive assessment: Always assess orientation, memory, attention — subcortical dementia pattern
Copper deposition in the proximal renal tubules causes generalized proximal tubular dysfunction (Fanconi syndrome):
- Aminoaciduria — increased amino acids in urine
- Glycosuria — urine glucose without hyperglycemia
- Phosphaturia → hypophosphatemia → rickets/osteomalacia
- Uricosuria → hypouricemia (serum uric acid is characteristically low in WD)
- Renal tubular acidosis (Type 2 — proximal)
- Hematuria, proteinuria
Low serum uric acid is a clue that should raise suspicion for WD.
🔬 Investigations — Exam Q&A
| Investigation | Expected Finding in WD |
|---|---|
| LFTs (ALT, AST, ALP, Bilirubin) | Elevated transaminases; ALP often paradoxically LOW in acute WD/ALF (copper inhibits ALP) |
| Serum ceruloplasmin | < 20 mg/dL (normal: 20–40 mg/dL) |
| Serum copper (total) | Low (due to low ceruloplasmin); free/non-ceruloplasmin copper elevated |
| 24-hr urinary copper | > 100 µg/day (normal <40 µg/day); in children >40–80 µg/day considered borderline |
| CBC | Hemolytic anemia (↓Hb, ↑reticulocytes), thrombocytopenia, leukopenia (hypersplenism) |
| PT/INR | Prolonged (hepatic synthetic dysfunction) |
| Direct Coombs test (DAT) | NEGATIVE — key finding in Wilsonian hemolysis |
| Serum uric acid | Low (uricosuria from Fanconi) |
| Urine: glucose, protein, amino acids | Glycosuria, aminoaciduria (Fanconi) |
In most causes of acute liver failure (viral, drug-induced), ALP is markedly elevated. In Wilsonian ALF, ALP is characteristically low or normal.
Reason: Copper inhibits bone/liver alkaline phosphatase activity. Additionally, the rapid massive hepatocyte destruction releases large amounts of copper, further suppressing ALP.
Clinical pearl: In a child with ALF, Coombs-negative hemolysis, and low ALP — think Wilson disease first. An ALP:total bilirubin ratio of < 2 (ALP in IU/L, bilirubin in µmol/L) or < 4 (bilirubin in mg/dL) is highly suggestive of Wilsonian ALF.
The D-penicillamine challenge test is used in children with borderline urinary copper (40–100 µg/day) to enhance copper mobilization.
Method: Collect baseline 24-hr urine copper. Then give oral D-penicillamine 500 mg at the start and again 12 hours into the collection period. Collect 24-hr urine copper.
Interpretation:
- Urinary copper > 1600 µg/24 hr after penicillamine challenge → strongly supports WD (in children)
- Normal individuals show minimal increase (< 200 µg/day)
Note: This test is primarily used in pediatric patients. Not validated in adults. Not used if patient is already on chelation therapy.
The Leipzig Score is a diagnostic scoring system for Wilson disease, developed at the 8th International Meeting on WD in Leipzig (2001), incorporated into EASL guidelines.
| Criterion | Finding | Points |
|---|---|---|
| KF Rings (slit-lamp) | Present | +2 |
| Absent | 0 | |
| Neurological symptoms | Severe | +2 |
| Mild | +1 | |
| Serum ceruloplasmin | Normal (>20 mg/dL) | 0 |
| 10–20 mg/dL | +1 | |
| <10 mg/dL | +2 | |
| Coombs-negative hemolytic anemia | Present | +1 |
| 24-hr urinary copper (no chelation) | 1–2× ULN (40–80 µg/day) | +1 |
| >2× ULN (>80 µg/day) | +2 | |
| Liver biopsy hepatic copper | 50–250 µg/g dry wt | +1 |
| >250 µg/g dry wt | +2 | |
| Normal (<50 µg/g) or rhodanine-negative | −1 | |
| ATP7B mutation analysis | Both mutations identified | +4 |
| One mutation identified | +1 |
✅ Interpretation
- ≥ 4 points: WD diagnosis established
- 3 points: WD possible — further investigations required
- ≤ 2 points: WD diagnosis unlikely
Liver biopsy is the most sensitive investigation for Wilson disease and shows:
- Hepatic copper content:
- > 250 µg/g dry weight → diagnostic of WD (normal <50 µg/g)
- Measured by quantitative copper estimation (not routine staining)
- Histological features: Steatosis (early), glycogenated nuclei, hepatitis, fibrosis, cirrhosis (late)
- Copper staining: Rhodanine or Orcein staining — detects copper granules in hepatocytes (present but not always diagnostic as distribution is uneven)
- Early: fat accumulation similar to NAFLD
- Late: Macronodular cirrhosis
Note: A normal hepatic copper content does NOT exclude WD (sampling error in uneven distribution).
MRI brain is the investigation of choice for neurological WD:
- T2/FLAIR hyperintensities in the putamen, globus pallidus, thalamus (bilateral, symmetric)
- Involvement of mesencephalon (midbrain), pons, and dentate nucleus of cerebellum
- "Face of the giant panda" sign on axial T2 MRI midbrain — high signal in tegmentum with low signal in red nucleus + preservation of colliculi = classic (rare but pathognomonic)
- "Face of mini panda" — in the pons (pontine tegmentum changes)
- T1 hypointensity in affected areas
- Cerebral atrophy in advanced cases
Serum ceruloplasmin can be falsely normal or elevated (up to 20–30 mg/dL) in WD in these situations:
- Acute phase reaction: Ceruloplasmin is an acute phase reactant — inflammation, infection, or pregnancy can raise levels even in WD
- Acute liver failure: Massive hepatocyte necrosis releases stored ceruloplasmin
- Estrogen use (OCP) — raises ceruloplasmin
Conversely, ceruloplasmin can be low without WD in: protein-losing states (nephrotic syndrome, protein-losing enteropathy), Menkes disease (X-linked copper deficiency), severe malnutrition.
Therefore, ceruloplasmin alone is never sufficient to diagnose or exclude WD.
The New Wilson Index (NWI), a revised King's score developed by Dhawan et al., predicts mortality in Wilsonian acute liver failure without liver transplantation.
Parameters scored: Serum bilirubin, INR (PT), WBC count, AST, and albumin.
- Score ≥ 11: High risk of death without liver transplantation → urgent LT listing
- Score < 11: May survive with medical management
It is more sensitive and specific than the original King's score for predicting mortality in pediatric Wilsonian ALF.
💊 Management — Exam Q&A
Management of WD has two goals: (1) Remove excess copper already deposited and (2) Prevent re-accumulation. Treatment is lifelong.
- Dietary copper restriction (adjunct)
- Pharmacological: Chelating agents (D-penicillamine, Trientine) OR Zinc salts
- Liver transplantation — for acute liver failure or decompensated cirrhosis not responding to medical therapy
- Monitoring of treatment efficacy and adverse effects
🚨 Critical Point
Discontinuation of treatment at any time — even after years of stable disease — can cause rapid, fatal deterioration. Treatment must never be stopped except after successful liver transplantation.
D-penicillamine is the first-line copper chelating agent for symptomatic Wilson disease.
Mechanism: Binds free copper in tissues and plasma → forms stable copper-penicillamine complex → excreted in urine (cupruresis)
Dose: 20 mg/kg/day (children), given in 2–3 divided doses, 30–60 min before meals. Maximum: 1500 mg/day.
Always co-prescribed with: Pyridoxine (Vitamin B6) 25–50 mg/day (penicillamine is an anti-pyridoxine agent)
Side effects:
- Early (within 1–3 weeks): Hypersensitivity — fever, rash, lymphadenopathy, leukopenia, thrombocytopenia → stop drug temporarily
- Neurological worsening: Paradoxical neurological deterioration in ~25% of neurological WD patients (copper is rapidly mobilized from liver to brain)
- Late: Nephrotic syndrome, SLE-like syndrome, myasthenia gravis, elastosis perforans serpiginosa, pemphigus, Goodpasture syndrome
- Nephrotoxicity, bone marrow suppression
Trientine (triethylenetetramine dihydrochloride, TETA) is a copper chelating agent used as an alternative to D-penicillamine.
| Feature | D-Penicillamine | Trientine |
|---|---|---|
| Mechanism | Chelation → urinary excretion | Chelation → urinary excretion |
| Efficacy | High | Similar (slightly less) |
| Side effects | Significant | Fewer — safer profile |
| Neurological paradox | More common (25%) | Less common |
| Pyridoxine | Required | Not required |
| Use | First-line (traditional) | Preferred if intolerant to D-pen; neurological WD |
| Cost | Cheaper | More expensive |
Dose: 20 mg/kg/day in 2–3 divided doses before meals.
Mechanism: Zinc induces metallothionein synthesis in intestinal enterocytes → metallothionein binds dietary copper in the intestinal cell → copper is lost when enterocytes shed (reduced copper absorption). Zinc also induces metallothionein in liver cells.
Uses:
- Maintenance therapy after initial chelation has reduced copper load
- Asymptomatic patients (presymptomatic siblings identified on screening)
- Pregnant women with WD (safe in pregnancy; chelators teratogenic in high doses)
Dose: Zinc sulfate or acetate — 75 mg elemental zinc/day in children; 150 mg/day in adults (given in 3 divided doses, 1 hr before meals)
Side effects: Gastric irritation (most common), reversible sideroblastic anemia (rare), may impair immune function at very high doses
NOT used as first-line in symptomatic/acute WD — onset of action too slow.
Dietary restriction of copper is an adjunct (not a primary treatment):
Foods to avoid (high copper content):
- Shellfish (oysters, lobster, crab)
- Organ meats (liver, kidney)
- Nuts and seeds (cashews, sunflower seeds)
- Chocolate, cocoa
- Mushrooms
- Dried legumes, whole grains
Water: If tap water flows through copper pipes, drink only filtered or bottled water (especially in first year of diagnosis)
Note: Dietary restriction alone cannot maintain copper balance in WD — pharmacological therapy is essential.
Indications for liver transplantation in WD:
- Wilsonian Acute Liver Failure (ALF): New Wilson Index ≥ 11 → urgent transplant listing
- Decompensated cirrhosis not responding to adequate medical therapy (chelation/zinc) for at least 2–3 months
- Some cases of severe neurological WD not responding to chelation (controversial; LT not routinely recommended for pure neurological WD)
Outcome after transplant: Liver transplantation is curative for hepatic WD. The ATP7B gene in the transplanted liver functions normally → copper metabolism normalizes → chelation therapy can be stopped.
KF rings: Gradually disappear over months–years after transplantation.
Contraindication: Severe irreversible neurological damage is a relative contraindication for transplant (neurological symptoms may persist or worsen).
Response to treatment is monitored by:
- 24-hr urinary copper: Should increase initially (mobilization of copper), then decrease to < 100–500 µg/day on chelation; aim for < 75 µg/day on zinc maintenance
- Serum free copper (non-ceruloplasmin-bound copper): Should normalize (< 15 µg/dL)
- LFTs: Should improve over 6–12 months
- Neurological assessment: Symptoms may take 6–24 months to improve
- KF rings: Fade over months–years
Monitoring for drug toxicity:
- D-penicillamine / Trientine: CBC, urine protein — every 2 weeks initially, then every 3–6 months
- Zinc: Serum zinc levels; CBC (for sideroblastic anemia)
Over-chelation signs: Excessive copper removal → copper deficiency → neurological worsening, sideroblastic anemia, neutropenia. Urinary copper < 25 µg/day on chelation suggests over-chelation.
WD is autosomal recessive. Each sibling of an index case has a 1 in 4 (25%) chance of being affected.
Screening approach:
- Slit-lamp examination for KF rings
- Serum ceruloplasmin
- 24-hr urinary copper
- LFTs
- ATP7B mutation analysis — most reliable; test for the specific mutations identified in the index case
If sibling is affected (even asymptomatic): Start treatment — zinc salts are preferred in presymptomatic children as they are safer and prevent symptom onset.
Early treatment in presymptomatic patients leads to near-normal life expectancy.
🔭 Recent Advances — Exam Q&A
Relative Exchangeable Copper (REC) is the proportion of free (labile, non-ceruloplasmin-bound) copper relative to total serum copper, expressed as a percentage.
Formula: REC = (Exchangeable copper / Total serum copper) × 100
- Normal: < 5–8%
- Wilson disease: typically > 15–18%
Advantages over traditional tests:
- Useful in patients with normal or borderline ceruloplasmin
- Valuable in diagnosing WD presenting as acute liver failure (where ceruloplasmin may be falsely elevated)
- Being incorporated into revised EASL 2024 guidelines as an additional diagnostic criterion
- Can help identify WD even in young children (< 5 years) before classical features develop
- Tetrathiomolybdate (TM) — Ammonium Tetrathiomolybdate (ATM):
- Mechanism: Forms tripartite complex with copper and albumin in the gut → prevents copper absorption; also chelates systemic copper
- Advantage: Lower risk of neurological worsening than D-penicillamine
- Currently in clinical trials (ATLAS trial, WilsonReg study)
- Bis-choline tetrathiomolybdate (WTX101/Decuprate) — oral formulation under Phase 3 trials for neurological WD
- Methanobactin: Small molecule copper chelator from methanotropic bacteria — high copper specificity; in preclinical studies
- Hepatocyte transplantation: Transplanting normal ATP7B-expressing hepatocytes — animal model success; early human studies
Gene therapy aims to deliver a functional copy of the ATP7B gene to hepatocytes to restore copper transport.
- Vector used: AAV (Adeno-associated virus) vectors — primarily AAV8 and AAV9, with high liver tropism
- Has shown effectiveness in animal models of WD (Long-Evans Cinnamon rats, tx-j mice)
- Challenge: The ATP7B gene is large (~4.4 kb coding sequence) — exceeds the packaging capacity of single AAV vectors; dual-vector systems are being explored
- Phase 1/2 clinical trials are ongoing (e.g., UX701 by Ultragenyx)
- Not yet in clinical practice but holds promise as a curative single-dose treatment
- Relative Exchangeable Copper (REC) incorporated as additional diagnostic tool alongside Leipzig score
- Trientine now recommended as equivalent first-line agent to D-penicillamine for symptomatic WD (not just second-line), especially for neurological WD
- Emphasis on ATP7B genetic testing as part of routine diagnostic workup
- Neurological WD: Trientine or chelation combined with zinc is preferred over D-penicillamine alone to minimize neurological worsening
- Pregnancy: Zinc salts are safe and preferred; chelators should be continued at reduced dose (not stopped)
- Liver transplantation for neurological WD: only in selected cases; pure neurological WD without liver disease is generally NOT an indication
- Tetrathiomolybdate: Mentioned as an emerging alternative, especially for neurological presentations
WD patients can have successful pregnancies with appropriate management. Untreated WD leads to infertility, miscarriage, and fetal loss.
Management in pregnancy:
- Do NOT stop treatment during pregnancy — stopping can cause acute hepatic decompensation and death
- Zinc salts: Drug of choice in pregnancy — safe, effective for maintenance, no teratogenicity
- D-penicillamine: If patient was on D-penicillamine, reduce dose by 25–50% in the third trimester (impairs wound healing at delivery); switch to zinc if possible
- Trientine: Data more limited; reduce dose in third trimester
- Avoid high-copper foods
- Monitor copper status each trimester
⚡ Key Points — Quick Revision
One-Liners for Exam
- Gene: ATP7B (chromosome 13q14.3) — autosomal recessive
- Defect: Failure of hepatic copper excretion into bile + defective ceruloplasmin synthesis
- Age of presentation: 5–35 years; children → hepatic first
- Most common presentation in children: Hepatic (85% cases)
- Pathognomonic ocular sign: Kayser-Fleischer rings (slit-lamp) — always present in neurological WD
- Classic neurological sign: Wing-beating tremor
- Serum ceruloplasmin: < 20 mg/dL (low)
- 24-hr urinary copper: > 100 µg/day (high)
- ALP in Wilsonian ALF: Paradoxically LOW (copper inhibits ALP)
- Hemolysis in WD: Coombs-NEGATIVE (non-immune, copper-mediated)
- Low serum uric acid: Clue to Fanconi syndrome in WD
- Liver biopsy: Hepatic copper > 250 µg/g dry weight → diagnostic
- Leipzig score ≥ 4: WD established; 3 = possible; ≤ 2 = unlikely
- "Face of giant panda" sign: MRI midbrain — pathognomonic for neurological WD
- D-penicillamine: First-line chelator; give with pyridoxine (Vit B6); risk of neurological worsening 25%
- Trientine: Fewer side effects than D-penicillamine; preferred in neurological WD
- Zinc salts: Maintenance / presymptomatic / pregnancy — NOT for acute symptomatic WD
- D-penicillamine challenge test: Urine copper > 1600 µg/24hr in children → supports WD
- Sunflower cataract: Copper in lens — does not impair vision; regresses with treatment
- Treatment is lifelong: Stopping treatment can be fatal
- Liver transplant: Curative for hepatic WD; not routinely for pure neurological WD
- New Wilson Index ≥ 11: Urgent liver transplant in Wilsonian ALF
- Sibling screening: Mandatory — 25% risk; treat even if asymptomatic
- REC (Relative Exchangeable Copper): > 15% → strongly suggests WD; new diagnostic marker
- Pregnancy: Zinc salts are safest; never stop all treatment
🔑 Differentials to Know
- Chronic hepatitis B/C — serology positive; no KF rings
- Autoimmune hepatitis — ANA/ASMA positive; ceruloplasmin normal; Coombs positive hemolysis
- Non-alcoholic fatty liver disease — metabolic features; normal copper studies
- Alpha-1 antitrypsin deficiency — low A1AT levels; PiZZ phenotype; no KF rings
- Menkes disease — X-linked recessive; low serum copper AND ceruloplasmin; presents in infancy with neurodegeneration, kinky hair; opposite to WD (copper deficiency disorder)