1. Dr. M. SOFI MD; FRCP (London); FRCPEdin; FRCSEdIn
WILSON’S DISEASE
Dr. M. SOFI MD; FRCP (London); FRCPEdin; FRCSEdIn

2. WILSON’S DISEASE
Wilson disease is a rare autosomal recessive inherited disorder of copper metabolism that is characterized by excessive deposition of copper in the liver, brain, and other tissues. Wilson disease is often fatal if not recognized and treated when symptomatic.
Wilson disease biopsy specimen with rhodanine stain (stain specific for copper deposition).

3. Signs and symptoms May lead to fulminant liver failure Encephalopathy
Hepatic dysfunction is the presenting feature in more than half of patients.
3 major patterns of hepatic involvement are as follows:
Chronic active hepatitis
Cirrhosis (the most common initial presentation)
Fulminant hepatic failure
May lead to fulminant liver failure
Encephalopathy
Cerebral edema: Signs of increased intracranial pressure(eg, papilledema, hypertension, bradycardia)
Jaundice: Often present but not always
Ascites: Potential for hepatic vein thrombosis with rapid development of fulminant hepatic failure
Change in liver span: May be small due to hepatic necrosis 

4. Signs and symptoms Neuropsychiatric features
Most patients who present with neuropsychiatric manifestations have cirrhosis. The most common presenting neurologic feature is asymmetric tremor, which is variable in character and may be predominantly resting, postural, or kinetic.
Frequent early symptoms include the following:
Difficulty speaking
Excessive salivation
Ataxia
Mask like facies
Clumsiness with the hands
Personality changes

5. Signs and symptoms Late manifestations: Dystonia Spasticity
Grand mal seizures
Rigidity
Flexion contractures
Psychiatric features (10-20% of patients) include:
Emotional lability
Impulsiveness
Disinhibition
Self-injurious behavior
Psychiatric abnormalities associated with Wilson disease has been divided into the following 4 basic categories:
Behavioral
Affective
Schizophrenic-like
Cognitive

6. Signs and symptoms Musculoskeletal manifestations
The arthropathy of Wilson disease resembles premature osteoarthritis
Symptomatic joint disease late in the course of the disease, frequently after age 20 years
The arthropathy generally involves the spine and large appendicular joints (e.g., knees, wrists, hips)
Osteochondritis dissecans, chondromalacia patellae, and chondrocalcinosis have also been described
Hematologic and renal manifestations
Coombs-negative acute intravascular hemolysis (10-15%)
Urolithiasis
Hematuria

7. Signs and symptoms
Kidneys: renal tubular acidosis (Type 2), a disorder of bicarbonate handling by the proximal tubules leads to:
Nephrocalcinosis (calcium accumulation in the kidneys)
Weakening of bones (due to calcium and phosphate loss),
Aminoaciduria
Heart: cardiomyopathy is a rare
but recognized problem in
Wilson's disease; it may lead to: 
Heart failure
Cardiac arrhythmias
Endocrine:
Hypoparathyroidism 
leading to low calcium levels) 
Infertility 
Habitual abortion

8. Signs and symptoms Kayser-Fleischer rings
Formed by the deposition of copper in the Descemet membrane in the limbus of the cornea
The color may range from greenish gold to brown
Well-developed rings may be readily visible to the naked eye or an ophthalmoscope set at +40
Kayser-Fleischer rings
Identified using slit-lamp examination or gonioscopy
Present in 90% of individuals with symptomatic WD invariably present in those with neurologic manifestations
Not pathognomonic of WD unless accompanied by neurologic manifestations, as may observed in patients with chronic cholestatic disorders

9. Ophthalmologic examination revealed the presence of bilateral Kayser–Fleischer rings, most prominently seen laterally (arrows).

10. Wilson’s disease: Diagnosis
Serum ceruloplasmin levels are less than 20 mg/dL (NR: mg/dL) approximately 90% of all patients with WD
The urinary copper excretion rate is greater than 100 mcg/day (NR: < 40 mcg/day) but it may be elevated in other cholestatic liver diseases
Patient with Kayser-Fleischer rings, a serum ceruloplasmin level < 10 mg/dL and 24-hour urine copper excretion >40 mcg/day establish the diagnosis of Wilson disease
Hepatic copper on a liver biopsy specimen is >250 mcg/g of dry weight even in asymptomatic patients
Normal result (15-55 mcg/g) effectively excludes the diagnosis of untreated WD
Genetic testing is limited to screening of family members for an identified mutation detected in the index patient

11. MRI Brain: Wilson disease
Hyperintensity in lentiform nuclei and mesencephalic regions on T1 have been described as most common initial MRI abnormality  
T2 hyperintensity is also seen typically involving basal ganglia:
Putamen
Globus pallidus
Caudate nucleus
Thalamus:
ventrolateral aspect

12. T2-weighted axial MRI demonstrates the “face of the giant panda” in the midbrain (arrow).

13. Wilson’s disease: Diagnostic evaluation
WD should be considered in any individual between the ages of 3 and 55 years with liver abnormalities of uncertain cause.
WD must be excluded in any patient with unexplained liver disease along with neurological or neuropsychiatric disorder
In a patient in whom WD is suspected, KayserFleischer rings should be sought by slit-lamp examination by a skilled examiner.
The absence of KayserFleischer rings does not exclude the diagnosis of WD, even in patients with predominantly neurological disease

14. Wilson’s disease: Management
The mainstay of therapy is lifelong use of chelating agents (eg, penicillamine, trientine)
Symptoms, particularly neurologic ones, may worsen with initiation of chelation
Surgical decompression or transjugular intrahepatic shunting (TIPS) is reserved for recurrent or uncontrolled variceal bleeding
Orthotopic liver transplantation is curative
Other treatments for Wilson disease include the following:
Anticholinergics, baclofen, GABA antagonists, and levodopa to treat parkinsonism and dystonia
Antiepileptics to treat seizures
Neuroleptics to treat psychiatric symptoms
Protein restriction, lactulose, or both to treat hepatic encephalopathy

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