Description

• Autosomal recessive condition affecting copper excretion; originally known as progressive lenticular degeneration
• Leads to progressive liver damage and cirrhosis, commonly associated with neuropsychiatric sequelae from systemic copper deposition

Epidemiology

Incidence
~2 to 4 cases per 100,000 live births

Prevalence

• Estimated prevalence 1/10,000 to 30,000 worldwide (1)
• Higher prevalence with consanguinity
• Equal prevalence between men and women, although women have higher likelihood of developing hepatic failure (approximately 4:1)
• Men more likely to develop neuropsychiatric disease

Etiology and Pathophysiology

• Average copper in diet is 2 to 5 mg/day, with recommended intake approximately 0.9 mg/day (2).
• Copper is normally absorbed in the duodenum and transported to liver with excess copper excreted into bile.
• Copper in serum is bound to amino acids and albumin because it is toxic in its free form through oxidation.
• Gene ATP7B encodes a metal-transporting ATPase which excretes copper into bile.
• Reduced or absent ATPase protein leads to copper accumulation in hepatocytes causing injury, along with impaired ability to incorporate copper into ceruloplasmin (decreased half-life of ceruloplasmin) (2).
• Systemic deposition is noted with copper in bloodstream.

Genetics

• Copper-transporting ATPase is encoded on ATP7B gene located on chromosome 13q.
• Most common mutation is H1069Q in 10–40% of patients.
• Autosomal recessive inheritance pattern
• Heterozygous carrier rate is ~1:100 to 200.

Risk Factors

• Consanguinity increases risk of genetic mutation (1).
• First-degree relatives with Wilson disease

General Prevention

• Screening recommended in first-degree relatives of patients with known Wilson disease
• Typically conducted around ages 3 to 5 years

Commonly Associated Conditions

No other phenotype is known to be associated with ATP7B mutation at this time (3).