Aka Hepatolenticular degeneration
Autosomal Recessive inheritance
What is the defect in Wilson disease?
Basic defect in hepatocellular copper transport, leading to the accumulation of copper in the liver and other tissues, including the brain.
ATP7B is a copper-transporting intracellular protein affected in Wilson disease. ATP7B is expressed mainly in hepatocytes.
This defect leads to reduced incorporation of copper into apo ceruloplasmin and decreased transport of copper from the liver into bile, leading to copper excess in tissue.
Although the ceruloplasmin levels are diagnostic in Wilson disease it does not play any significant role in the disease pathogenesis.
Note: Hereditary aceruloplasminemia is a disease condition characterized by iron deposition in tissues and not copper
How copper deposition occurs in other tissues?
Once the hepatocytes are filled with copper this leads to injury thus liberating the copper in circulation which leads to extrahepatic copper deposition.
Wilson disease present with hepatic, neurological and psychiatric manifestations.
Children usually tend to present more commonly with hepatic symptoms whereas adolescent and older patients have neurological manifestations
What are the hepatic manifestations?
Hepatic manifestations can be asymptomatic with biochemical abnormalities or acute hepatic failure or acute hepatitis or chronic hepatitis and cirrhosis.
Patients of Wilson disease presenting with acute liver failure have often associated Coombs negative hemolysis.
How is acute hepatitis of Wilson different from infective hepatitis?
Presence of coombs negative hemolytic anemia
Aminotransferases are elevated but as significant as infective hepatitis. AST:ALT >2
ALP is normal or subnormal. ALP:total bilirubin <4
What are the neurological manifestations of Wilson disease?
Basal ganglia is affected in case of Wilson disease.
Dysarthria is the most common neurological manifestation of Wilson disease.
Other manifestations can be
Cognitive impairment - can be frontal syndrome or subcortical dementia
KF ring or Kayser-Fleischer rings are present in 98% of neurological Wilson.
What are KF rings?
Ocular manifestation of Wilson.
Present in 50% of hepatic Wilson and 98% of neurological forms.
It is an indicator of CNS copper deposition.
These are brownish deposits of Copper in Descemet's membrane.
Slit lamp is required for visualizing but sometimes can be visible with naked eyes.
It is an important clinical clue for Wilson diagnosis.
What other ocular manifestation is visible in Wilson?
Sunflower cataract sue to copper deposition in lens.
What is the type of hemolysis seen in Wilson?
Coombs negative hemolysis
What are the renal manifestations of Wilson Disease?
Fanconi syndrome characterized by loss of amino acids, bicarbonate, glucose and proximal renal tubular acidosis
Also, nephrolithiasis may occur secondary to distal renal tubular acidosis
Diagnosis of Wilson disease
|Source: ESPGHAN Wilson guidelines 2018|