1. Wilson’s Disease, A Disease to know Abdulwahab Telmesani FRCPC,FAAP Faculty of Medicine and Medical Science Umm Al-Qura University

2. Case 1 A previously healthy, 9-year-old, right-handed Female developed 2 episodes of focal seizure with Todd’s paralysis Martha D. Carlson Ped Neuro 2003

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

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

5. 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.

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

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

8. Case 2 An 18 years old male with the symptoms; Suicidal ideas Depressed mood Psychomotor slowing Stuttering

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

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

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

12. Diagnosed as Wilson’s Disease. Symptoms improved on D – Penicillamine Patrick Stiller J Psych. Neurosci 2002

13. Case 3 19 year female diagnosed and treated as Schizophrenic for 2 years without benefit Patrick Stiller J Psych. Neurosci 2002

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

15. Laboratory investigation; @ Low cerulplasmin @ High serum copper @ Very high 24 HR urinary copper Patrick Stiller J Psych. Neurosci 2002

16. Treatment; @ Psychotherapy discontinued @ D-Penicillamine started @ Patient improved Patrick Stiller J Psych. Neurosci 2002

18. Wilson’s Disease Autosomal Recessive Disease The Gene ATP7B Mapped to chromosome 13

19. Wilson’s Disease Low cerulplasmin Copper deposition in; liver, brain, kidneys, eyes, heart, Hemolysis

20. Wilson’s Disease Glutathione in Hepatocytes protect against metal toxicity G6PD maintain Glutathione

21. Wilson’s Disease The age of presentation can vary from 4 to 60 years

22. 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)

23. Wilson’s Disease Presents in any of the following;

24. Wilson’s Disease Early symptoms are vague and non-specific; Lethargy Anorexia Abdominal pain Epistaxis

25. Hepatic WD Acute liver disease Chronic liver disease Acute hepatic failure

26. Neuro./Psych. WD Minimal neurological manifestations Sever neurological manifestations Psychiatric symptoms

27. Other WD presentations Renal tubular acidosis Bony deformities Hemolytic anemia

28. Uncommon manifestations hypercalciuria nephrocalcinosis, chondrocalcinosis osteoarthritis, sunflower cataracts cardiac manifestations.

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

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

31. 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.

33. Wilson’s Disease Diagnosis

34. Wilson’s Disease Liver biopsy and determination of hepatic copper (Copper/gram dried liver tissue) is the golden standard for the diagnosis of Wilson’s Disease

35. Wilson’s 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

36. Wilson’s Disease MRI for Diagnosis and Follow up

37. Wilson’s Disease In the neuro. WD MRI shows lesions in the basal ganglia, cerebral white matter, midbrain, pons and cerebellum

38. Hyperintensity in globus pallidus in a 20-year-old female with the initial phase of the hepatic form of Wilson’s

39. Wilson’s Disease MRI findings are reversible after treatment

41. Wilson’s Disease How about the patient with acute hepatic failure, liver biopsy is not possible and other lab investigations are affected by the liver disease?

42. Alkaline phosphatase to total bilirubin ratio showed a good Discriminative power in differentiating Fulminant Wilson’s disease from Fulminant hepatic failure of other causes, and a ratio <1 showed a 86% sensitivity and 50% specificity for Fulminant Wilson’s disease diagnosis. Pierre Tissières, MD; Pediatr Crit Care Med 2003

43. Wilson’s 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

44. Wilson’s Disease Treatment; D- Penicillamine Trientine Tetrathiomolybdate Zinc

45. The future gene replacement therapy gene repair Hepatocytes transplantation

46. 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?

47. Q; How many of FTT patients are Wilson's Disease? How many of the undiagnosed hemolytic anemia patients are Wilson's Disease? How many …?