Wilson’s Disease
(Hepatology. 2003;37:1475-92)
DEFINITION:
Autosomal recessive inherited disorder of copper overload secondary to deficiency of an enzyme derived from liver cells (↓ secretion)
Other inheritable forms of liver disease: α1-AT, Hemochromatosis
EPIDEMIOLOGY:
1 in 30,000 is homozygous and 1 in 100 is a heterozygous carrier
Usually manifests before age 30; almost always before 40
ETIOLOGIES:
Autosomal recessive; Gene located on chromosome 13, codes for P-type adenosine triphosphatase, a copper-transport protein
Most likely causes a defect in transfer of hepatocellular lysosomal copper into bile, thereby resulting in copper retention
i.e. impaired copper secretion into the bile, thereby resulting in copper retention
PATHOPHYSIOLOGY:
Impaired copper transport and secretion (Hereditary Hemochromatosis is increased iron absorption)
Copper homeostasis is achieved via biliary secretion; Intestinal absorption is normal but biliary secretion is decreased
↓ ceruloplasmin is not the cause of Wilson’s rather it is an effect of the abnormal cellular trafficking of copper
ATP-7B gene involved, located on chromosome 13
The number of clinically important mutations makes genetic testing less useful (as opposed to genetic testing for HH)
CLINICAL MANIFESTATIONS/PHYSICAL EXAM:
May be completely asymptomatic or have devastating neurological symptoms
Copper retention in liver:
Chronic hepatitis and cirrhosis, rarely fulminant hepatic failure (♀ > ♂) which is uniformly fatal without transplant
Always get a ceruloplasmin in young people with hepatitis or steatosis
Copper retention in CNS/Neuro:
Neuro psych disorders: psychosis/depression
Tremor, ataxia
Kayser-Fleischer rings in eyes (copper deposition in periphery of cornea) or sunflower cataracts (do not interfere with vision)
Dementia
Hemolytic anemia (coombs negative)
Other systems involved: Joints (arthropathy), Kidneys (nephrolithiasis), blue discoloration of base of fingernails (Azure lunulae) is rare
*Always have high index of suspicion in patient with unexplained hepatic, neurological or psychiatric disease*
LABORATORY STUDIES:
If ↓ ceruloplasmin or ↑ 24 hr urine copper = liver biopsy for histology and quantitative copper determination
↓ serum ceruloplasmin (copper binding protein); therefore ↑ serum & urinary copper
Diagnostic criteria (any one of below):
Ceruloplasmin <200 mg/L (normal is 230-500 mg/L or 21-45 mg/dL) and KF rings
Ceruloplasmin <200 mg/L and Hepatic copper content >250 mcg/gm dry weight on liver biopsy (normal is 38 mcg/gm)Related posts:
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