Wilsons disease
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Wilson’s Disease
Dr. Lokesh.SAssociate ProfessorDepartment of General Medicine
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Wilson’s DiseaseAutosomal Recessive DiseaseThe Gene ATP7B
Encodes metal-transporting ATPase Reduced hepatic excretion of copperCopper not incorporated into
ceruloplasminMapped to chromosome 13
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Wilson’s Disease Low cerulplasmin Copper deposition in; liver, brain, kidneys, eyes, heart, Hemolysis
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Wilson’s Disease Glutathione in Hepatocytes protect
against metal toxicity G6PD maintain Glutathione
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Wilson’s Disease
The age of presentation can vary from 4 to 60 years
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Wilson’s Disease
Presents in any of the following;
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Wilson’s 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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Wilson DiseaseNeuropsychiatric Manifestations
Netter’s Gastroenterology, 2nd ed., Elsevier Inc., 2010, all rights reserved
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Wilson DiseaseKayser-Fleischer Ring Copper deposited in Decemet’s membrane Slit lamp required in most patients with
suspected Wilson Disease 50-62% of patients with liver disease 95% of patients with neurologic disease Chronic cholestatic diseases associated
with K-F rings WD= K-F rings + low ceruloplasmin
Sternlieb I, Hepatology 1990;12: 1234-1239.
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Kayser-Fleischer Rings
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One of the most characteristic features of
Wilson’s disease is that no two patients,
Even within a family, are ever quite alike.
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There is likely an even larger range of phenotypic expression than we presently recognize.
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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 every
one after the ages of 3 to 5 years.
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Wilson’s Disease
Diagnosis
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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
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Wilson DiseaseHepatic Copper Concentration Diagnostic of WD: > 250g/g dry liver
wt. (nl. < 50 g/g) May be elevated in other liver diseases
Chronic cholestatic disorders Indian childhood cirrhosis
Heterogeneous distribution Obtained when diagnosis not clear
Merle U et al, Gut 2007;56:115-120.
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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
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Wilson’s Disease
MRI for Diagnosis and Follow up
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Wilson’s 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 Wilson’s
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Wilson’s Disease
MRI findings are reversible after treatment
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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?
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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.
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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
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Wilson’s Disease
Treatment; D- Penicillamine Trientine Tetrathiomolybdate Zinc
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The future
gene replacement therapy gene repair Hepatocytes transplantation