Wilson’s Disease, A Disease to know

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Wilsons Disease, A Disease to know

• Abdulwahab Telmesani
• FRCPC,FAAP
• Faculty of Medicine and Medical Science
• Umm Al-Qura University

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Case 1

• A previously healthy, 9-year-old, right-handed
• Female developed 2 episodes of focal seizure
• with Todds paralysis
• 
  Martha D. Carlson Ped
  Neuro 2003

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• L.P and CSF exam was normal
• CT scan was normal
• EEG was abnormal
• Started on antiepileptic therapy

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• MRI done after the 2nd episode of seizure showed
• Bilateral signal abnormalities in the basal
  ganglia,
• thalamus, and parietal lobe.

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• Hx showed change in her hand writing and speech
• Normal hepatic transaminase
• Low ceruloplasmin
• A low serum copper
• An extremely elevated 24-hour urine copper
• Ophthalmologic examination confirmed
  Kayser-Fleisher rings.

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• Treated with oral tetrathiomolybdate (anti-copper
  therapy).
• Followed by zinc maintenance.
• Clinically improved.

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• One-year follow-up MRI
• Improvement in the parietal, basal ganglia,
  and thalamic regions.
• 
  Martha D. Carlson Ped Neuro 2003

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Case 2

• An 18 years old male with the symptoms
• Suicidal ideas
• Depressed mood
• Psychomotor slowing
• Stuttering

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• Diagnosed as Schizophrenic
• Received 2 years of psychotherapy
• Patrick
  Stiller J Psych. Neurosci 2002

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• P/E
• No Kayser -Fleischer ring
• Normal physical examination
• 
  Patrick Stiller J Psych. Neurosci 2002

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• Laboratory investigation
• Low cerulplasmin
• high serum copper
• high 24 HR urine copper
• 
  Patrick Stiller J Psych. Neurosci
  2002

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• Diagnosed as Wilsons Disease.
• Symptoms improved on D Penicillamine
• Patrick
  Stiller J Psych. Neurosci 2002

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Case 3

• 19 year female diagnosed and treated as
• Schizophrenic for 2 years without benefit
• 
  Patrick Stiller J
  Psych. Neurosci 2002

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• On admission found to have
• _at_ Dysarthria
• _at_ Slow movement (rigidity)
• _at_ No Kayser -Fleischer ring
• Patrick
  Stiller J Psych. Neurosci 2002

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• Laboratory investigation
• _at_ Low cerulplasmin
• _at_ High serum copper
• _at_ Very high 24 HR urinary copper
• 
  Patrick Stiller J Psych. Neurosci 2002

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• Treatment
• _at_ Psychotherapy discontinued
• _at_ D-Penicillamine started
• _at_ Patient improved
• 
  Patrick Stiller J Psych.
  Neurosci 2002

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Wilsons Disease

• Autosomal Recessive Disease
• The Gene ATP7B
• Mapped to chromosome 13

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Wilsons Disease

• Low cerulplasmin
• Copper deposition in
• liver,
• brain,
• kidneys,
• eyes,
• heart,
• Hemolysis

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Wilsons Disease

• Glutathione in Hepatocytes protect against metal
  toxicity
• G6PD maintain Glutathione

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Wilsons Disease

• The age of presentation can vary from 4 to 60
  years

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• We just recently reported on two siblings who had
  
• identical ATP7B mutations that presented
• differently and were not diagnosed until their
• eighth decade of life
• 
  A. Ala, M.L. Schilsky / Clin Liver Dis
  (2004)

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Wilsons Disease

• Presents in any of the following

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Wilsons Disease

• Early symptoms are vague and non-specific
• Lethargy
• Anorexia
• Abdominal pain
• Epistaxis

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Hepatic WD

• Acute liver disease
• Chronic liver disease
• Acute hepatic failure

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Neuro./Psych. WD

• Minimal neurological manifestations
• Sever neurological manifestations
• Psychiatric symptoms

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Other WD presentations

• Renal tubular acidosis
• Bony deformities
• Hemolytic anemia

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Uncommon manifestations

• hypercalciuria
• nephrocalcinosis,
• chondrocalcinosis
• osteoarthritis,
• sunflower cataracts
• cardiac manifestations.

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• One of the most characteristic features of
• Wilsons disease is that no two patients,
• Even within a family, are ever quite alike.
• 
  P. FERENCI .
  Aliment Pharmacol Ther 2004

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• There is likely an even larger range
• of phenotypic expression than we
• presently recognize.
• 
  A. Ala, M.L. Schilsky / Clin Liver Dis
  (2004)

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Family screening

• A diagnosis of WD in an individual must
• alert the clinician to begin screening
• first-degree relatives of identified parents.
• Screening should be performed in very one
• after the ages of 3 to 5 years.
• 
  

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Wilsons Disease

• Diagnosis

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Wilsons Disease

• Liver biopsy and determination of hepatic copper
• (Copper/gram dried liver tissue) is the golden
  standard for the diagnosis of Wilsons Disease

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Wilsons Disease

• Diagnosis (neuro./ psych. WD) (strongly suggested
  ) based on at least two of the following
• Low serum Cerulplasmin
• High 24 HR urine copper
• K.F Ring
• Ashish
  Bavdekar J Gastr Hepat 2004

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Wilsons Disease

• MRI for Diagnosis and Follow up

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Wilsons Disease

• In the neuro. WD MRI shows lesions in the
  basal ganglia, cerebral white matter, midbrain,
  pons and cerebellum

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Hyperintensity in globus pallidus in a
20-year-old
female with the initial
phase of the hepatic form of Wilsons
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Wilsons Disease

• MRI findings are reversible after treatment

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Wilsons Disease

• How about the patient with acute hepatic failure,
• liver biopsy is not possible and other lab
• investigations are affected by the liver disease?

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• Alkaline phosphatase to total bilirubin ratio
  showed a good
• Discriminative power in differentiating Fulminant
  Wilsons
• disease from Fulminant hepatic failure of other
  causes, and a
• ratio lt1 showed a 86 sensitivity and 50
  specificity for
• Fulminant Wilsons disease diagnosis.
• 
  Pierre Tissières, MD
  Pediatr Crit Care Med 2003

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Wilsons Disease

• Diagnosis (acute hepatic failure) strongly
  suggested by the following
• Low Hgb (hemolysis)
• Bilirubin more than 6 times transaminases less
  than 4 times (AST more than ALT)
• Low Alkaline phosphates
• High serum Copper
• Low serum cerulopasmin in siblings
• 
  Ashish Bavdekar J Gastr Hepat 2004

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Wilsons Disease

• Treatment
• D- Penicillamine
• Trientine
• Tetrathiomolybdate
• Zinc

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The future

• gene replacement therapy
• gene repair
• Hepatocytes transplantation

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Q

• How many of the seizures patients are Wilson's
  Disease?
• How many of psychiatry patients are Wilson's
  Disease?
• How many of the undiagnosed liver disease
  patients are Wilson's Disease?

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Q

• How many of FTT patients are Wilson's Disease?
• How many of the undiagnosed hemolytic anemia
  patients are Wilson's Disease?
• How many ?
• How many ?
• How many ?