Wilson’s Disease

Pathophysiology

1) copper accumulation in the liver, corneas, brain, and kidneys owing to inadequate biliary copper excretion 2) two forms – fulminant and chronic 3) deficiency of plasma ceruloplasmin is characteristic

Signs and Symptoms

1) classic triad – chronic liver disease, Kayser-Fleischer corneal rings, tremor, or dystonia 2) choreiform movements 3) progressive neurologic disease without signs of liver disease 4) psychiatric illness (presenting sign in 20% of cases) 5) other sequelae of cirrhosis – asterixis, ascites, encephalopathy 6) sunflower cataracts

Characteristic Test Findings

Laboratory – 1) hepatic copper concentration > 250 micrograms/dry g is characteristic 2) decreased serum ceruloplasmin 3) increased serum AST and ALT (1300-1500 mu/L) 4) increased PT 5) greatly increased serum bilirubin 6) decreased serum copper 7) increased urinary copper 8) hemolytic anemia Slit-lamp examination – 9) Kayser-Fleischer rings

Histology/Gross Pathology

1) copper accumulation in Descemet’s membrane of cornea 2) usually macronodular cirrhosis but can be micronodular 3) racket-shaped mitochondria

Associated Conditions

1) cirrhosis 2) renal tubular acidosis with renal failure 3) gallstones 4) hemolytic anemia 5) Fanconi’s anemia 6) nephrolithiasis 7) arthritis (mainly large joints) 8) rhabdomyolysis 9) hypoparathyroidism 10) pancreatitis

Biochemistry

impaired uptake of copper inton ceruloplasmin with impaired copper excretion

Inheritance/Epidemiology

1) autosomal recessive 2) occurs in 1/30,000 3) defect is in gene ATP7B on chromosome 13 4) presents at ages 3-50 years (in children, usually with liver failure)

Treatment

Penicillamine (with pyroxidine) – 1) increases urinary copper excretion 2) may have initial worsening of neurologic symptoms Trien (trientine) 3) increases copper excretion, decreases copper absorption from intestines Oral zinc – 4) interferes with absorption from intestine Other – 5) ammonium tetraiomolybdate 6) antioxidants 7) dimercaprol

Tips for USMLE

1) Kayser-Fleischer rings – occur in Wilson’s disease, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, and familial cholestatic syndromes 2) absence of Kayser-Fleischer rings does not rule out Wilson’s 3) hepatomas are rare in Wilson’s 4) increased AST and ALT are much less than in fulminant viral hepatitis 5) the other “copper disease” is Menkes (X-linked disorder of intestinal copper transport) 6) Wilson’s syndrome (not disease) – clinical hypothyroidism in setting of normal thyroid function tests.

Related Posts

Alagille’s Syndrome