wilsons disease
TRANSCRIPT
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