Saturday, November 29, 2014

WILSON’S DISEASE

WILSON’S DISEASE

Kayser-Fleischer ring.



DEFINITION
Wilson’s disease is a disorder of copper transport with inadequate biliary copper excretion, leading to an accumulation of the metal in the liver, brain, kidneys, and corneas.


PHYSICAL FINDINGS AND CLINICAL PRESENTATION
Hepatic presentation

● Acute hepatitis with malaise, anorexia, nausea, jaundice, elevated transaminase, prolonged prothrombin time; rarely, fulminant hepatic failure

● Chronic active (or autoimmune) hepatitis with fatigue, malaise, rashes, arthralgia, elevated transaminase, elevated serum IgG, positive antinuclear antibody (ANA) and anti– smooth muscle antibody

● Chronic liver disease, cirrhosis with hepatosplenomegaly, ascites, low serum albumin, prolonged prothrombin time, portal hypertension

Neurologic presentation
● Movement disorder: tremors, ataxia
● Spastic dystonia: masklike facies, rigidity, gait disturbance,dysarthria, drooling, dysphagia


Psychiatric presentation
● Depression, obsessive-compulsive disorder, psychopathic behaviors

Other organs
● Hemolytic anemia
● Renal disease (e.g., Fanconi’s syndrome with hematuria, phosphaturia, renal tubular acidosis, vitamin D–resistant rickets)
● Cardiomyopathy
● Arthritis

● Hypoparathyroidism
● Hypogonadism


Physical fi ndings
● Ocular: the Kayser-Fleischer ring is a gold-yellow ring seen at the periphery of the iris (Fig. 40–3)
● Stigmata of acute or chronic liver disease
● Neurologic abnormalities: 


CAUSE AND PATHOGENESIS
● Dietary copper is transported from the intestine to the liver, where normally it is metabolized into ceruloplasmin. In Wilson’s disease, defective incorporation of copper into ceruloplasmin
and a decrease of biliary copper excretion lead to accumulation of this mineral.

● The gene for Wilson’s disease is located in chromosome 13.


DIFFERENTIAL DIAGNOSIS
● Hereditary hypoceruloplasminemia
● Menkes’ disease
● Consider the diagnosis of Wilson’s disease in all cases of acute or chronic liver disease in which another cause has not  been established.

● Consider Wilson’s disease in patients with movement disorders or dystonia, even without symptomatic liver disease.


LABORATORY TESTS
● Abnormal liver function tests (LFTs; note that AST may be higher than ALT)
● Low serum ceruloplasmin level (less than 200 mg/L)
● Low serum copper (less than 65 g/L)
● 24-hr urinary copper excretion more than 100 g (normal, less than 30 g); increases to more than 1200 g/24 hr after 500 mg of D-penicillamine (normal, less than 500 g/24 hr)
● Low serum uric acid and phosphorus
● Abnormal urinalysis (hematuria)


BIOPSY
● Early: steatosis, focal necrosis, glycogenated hepatocyte nuclei; may reveal infl ammation and piecemeal necrosis
● Late: cirrhosis 
● Hepatic copper content (less than 250 g/g of dry weight; normal is 20 to 50 g/g)

TREATMENT
● Penicillamine, trientine: chelator therapy
● Zinc: inhibits intestinal copper absorption
● Ammonium tetrathiomolybdate for neurologic symptoms
● Antioxidants
● Liver transplantation (for severe hepatic failure unresponsive to chelation)



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