Keyser-Fleischer rings

Wilson Disease

Clinical Characteristics
Ocular Features: 

The cornea and lens have visible copper deposition.  This is responsible for the classic (though non-pathognomonic) copper-colored Kayser-Fleischer ring in the cornea where evidence of copper deposition can be visualized in the posterior stroma and in the endothelium.  About 50-60% of patients at any point have evidence of such copper deposition but the number rises to 90% in patients with neurologic and psychiatric symptoms.  Copper deposition in the lens leads to a ‘sunflower’ or 'sunburst' cataract consisting of a greenish central disc in the anterior capsule with spoke-like radial cortical opacities.  Eye involvement in Wilson disease usually does not lead to significant impairment of vision.

Systemic Features: 

This is a disorder of copper metabolism.  It is associated with severe liver disease, often beginning with signs of recurrent jaundice, sometimes a hepatitis-like illness, and often culminating in liver failure.  Hepatobiliary malignancies are a significant risk, occurring in more than 1 percent of patients.  Neurologic toxicity leads to various movement disorders such as tremors, poor coordination, dystonia, and choreoathetosis.  Many patients have mental symptoms such as depression, neurotic behavior, and personality disturbances.  Some have a mask-like facies and pseudobulbar symptoms.  Symptoms can appear anytime from 3 years of age to over 50.  Other organs such as kidney, pancreas, heart and even joints may also be involved.

Patients often have a low serum ceruloplasmin, low copper levels, increased urinary excretion of copper, and increased concentration of copper in the liver.

Genetics

This is an autosomal recessive disorder caused by homozygous or doubly heterozygous mutations in the ATP7B gene (13q14.3).  Heterozygotes usually do not develop symptoms but may have reduced serum ceruloplasmin levels.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Zinc and/or copper chelating agents such as D-penicillamine or trientine have long been used with benefit but the treatment must be used throughout life.  Reduced copper intake may also be helpful.  An orthotopic liver transplant can prolong life in selected patients.

References
Article Title: 

Hepatobiliary malignancies in Wilson disease.

Pfeiffenberger J, Mogler C, Gotthardt DN, Schulze-Bergkamen H, Litwin T, Reuner U, Hefter H, Huster D, Schemmer P, Czlonkowska A, Schirmacher P, Stremmel W, Cassiman D, Weiss KH. Hepatobiliary malignancies in Wilson disease. Liver Int. 2014 Nov 4. [Epub ahead of print].

PubMed ID: 
25369181

A practice guideline on Wilson disease

Roberts EA, Schilsky ML; Division of Gastroenterology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada. A practice guideline on Wilson disease. Hepatology. 2003 Jun;37(6):1475-92. Erratum in: Hepatology. 2003 Aug;38(2):536.

PubMed ID: 
12774027
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