Wilsons disease

Wilson’s Disease

Dr. Lokesh.SAssociate ProfessorDepartment of General Medicine

Wilson’s DiseaseAutosomal Recessive DiseaseThe Gene ATP7B

Encodes metal-transporting ATPase Reduced hepatic excretion of copperCopper not incorporated into

ceruloplasminMapped 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

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.

Wilson DiseaseNeuropsychiatric Manifestations

Netter’s Gastroenterology, 2nd ed., Elsevier Inc., 2010, all rights reserved

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.

Kayser-Fleischer Rings

One of the most characteristic features of

Wilson’s disease is that no two patients,

Even within a family, are ever quite alike.

There is likely an even larger range of phenotypic expression than we presently recognize.

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.

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 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.

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

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.

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

Wilson’s Disease

Treatment; D- Penicillamine Trientine Tetrathiomolybdate Zinc

The future

gene replacement therapy gene repair Hepatocytes transplantation