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

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

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

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

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.

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

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

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

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

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

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

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

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

On admission found to Slow movement No Kayser -Fleischer ring Patrick Stiller J Psych. Neurosci 2002

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

Psychotherapy D-Penicillamine Patient improved Patrick Stiller J Psych. Neurosci 2002

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

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

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

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

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)

Wilson’s Disease Presents in any of the following;

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

Hepatic WD Acute liver disease Chronic liver disease Acute hepatic failure

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

Other WD presentations Renal tubular acidosis Bony deformities Hemolytic anemia

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

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

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

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.

Wilson’s Disease Diagnosis

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

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

Wilson’s Disease MRI for Diagnosis and Follow up

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

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

Wilson’s Disease MRI findings are reversible after treatment

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?

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

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

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

The future gene replacement therapy gene repair Hepatocytes transplantation

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?

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