Wilson’s Disease, A Disease to know

Abdulwahab TelmesaniFRCPC,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 2nd 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 2An 18 years old male with

the symptoms;Suicidal ideasDepressed moodPsychomotor slowingStuttering

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 have;

@ Dysarthria@ Slow movement (rigidity)@ No Kayser -Fleischer ring Patrick

Stiller J Psych. Neurosci 2002

Laboratory investigation;

@ Low cerulplasmin@ High serum copper@ Very high 24 HR urinary copper

Patrick Stiller J Psych. Neurosci 2002

Treatment;

@ Psychotherapy discontinued@ D-Penicillamine started@ 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 screeningfirst-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 DiseaseDiagnosis (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 …? How many …? How many …?