Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.
Wilson disease is a rare, autosomal recessive, inherited condition in which excess copper accumulates throughout the organs and tissues of the body, especially the liver, brain, and eyes. Dietary copper is absorbed by the intestines and transported to the liver via albumin where it is processed according to the body’s needs.1
Normally, functional ATP7B protein transports copper through hepatocyte membranes and secretes excess copper into the biliary system, where it is excreted from the body. This protein also attaches 6 copper molecules to apoceruloplasmin, converting it into functional ceruloplasmin. Ceruloplasmin transports these copper molecules through the bloodstream to other tissues and organs of the body that require copper for optimal functioning, especially the brain.2
In Wilson disease, these ATP7B proteins are dysfunctional, impairing copper metabolism and transport. Copper subsequently accumulates in the liver and eventually is deposited in other tissues and organs.1
Genetic Risk Factors
The single largest risk factor for Wilson disease is a family history of the disease, particularly if first-degree relatives (parents or siblings) exhibit symptoms. Wilson disease is inherited in an autosomal recessive pattern. Both parents must have abnormal copies of the ATP7B gene, resulting in a 25% chance of passing down the condition to each of their children. Once a member of the family is diagnosed with Wilson disease, it is highly recommended that each first-degree relative undergo diagnostic testing to confirm the presence of the condition, even if they are asymptomatic.3,4
If the pathologic variant of a patient is known, molecular genetic testing to detect specific variants in first-degree relatives (usually siblings) allows for early diagnosis and treatment initiation prior to the onset of symptoms for optimal outcomes. If the pathologic variant is not known, the usual biochemical testing for serum copper and ceruloplasmin levels, liver function, and urinary copper excretion, in addition to slit-lamp examination for Kayser-Fleischer rings and ultrasound imaging of the liver, are recommended.5
Carriers of only 1 abnormal ATP7B gene never manifest symptoms of Wilson disease and do not require treatment4; however, if individuals know that they are carriers, they should undergo genetic counseling with their partner prior to starting a family to understand the risks of passing the condition on to their children.
Prenatal genetic testing can confirm the presence of Wilson disease in the fetus. Some of these prenatal tests are noninvasive, using polymerase chain reaction (PCR) to detect mutated fetal alleles circulating in the maternal plasma. In a previous study, researchers developed the circulating single-molecule amplification and resequencing technology (cSMART) to quantify single allelic molecules within maternal plasma and performed Sanger and whole-exome sequencing to correctly identify familial ATP7B gene mutations in 4 pregnancies at risk of Wilson disease.6
Read more about Wilson disease genetics
Fulminant Hepatic Failure
Although the trigger for developing fulminant hepatic failure is unknown, women with Wilson disease are at a higher risk of developing fulminant hepatic failure, severe hemolytic crisis, and irreversible neurologic degeneration during pregnancy.5,7 Treatment using chelating agents may harm the fetus, so treatment should continue during pregnancy at lower, but effective, levels to manage the condition during pregnancy.5
The risk of fulminant hepatic failure is higher in patients under the age of 22 years and in female patients.8
Initially, it was believed that excess copper accumulation in the liver had protective effects against hepatocarcinogenesis.9,10 However, a growing body of evidence suggests that Wilson disease itself is a risk factor for developing hepatocellular carcinoma.9
Hepatocyte proliferation combined with hepatocyte damage caused by excess copper accumulation provide the necessary environment for the formation of liver tumors. Hepatocellular carcinoma screening is recommended for patients with Wilson disease who have cirrhosis and elevated serum alanine aminotransferase levels.11
- Gilroy RK. Wilson disease: etiology. Medscape. Updated February 14, 2019. Accessed September 19, 2022.
- Linder MC. Apoceruloplasmin: abundance, detection, formation, and metabolism. Biomedicines. 2021;9(3):233. doi:10.3390/biomedicines9030233
- Wilson’s disease. Mayo Clinic. March 7, 2018. Accessed September 19, 2022.
- Wilson’s disease in children: symptoms and treatment. Children’s Hospital of Pittsburgh. Accessed September 19, 2022.
- Weiss KH. Wilson disease. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2022. October 22, 1999. Updated July 29, 2016. Accessed September 19, 2022.
- Lv W, Wei X, Guo R, et al. Noninvasive prenatal testing for Wilson disease by use of circulating single-molecule amplification and resequencing technology (cSMART). Clin Chem. 2015;61(1):172-181. doi:10.1373/clinchem.2014.229328
- Shimono N, Ishibashi H, Ikematsu H, et al. Fulminant hepatic failure during perinatal period in a pregnant woman with Wilson’s disease. Gastroenterol Jpn. 1991;26(1):69-73. doi:10.1007/BF02779512
- Stremmel W, Merle U, Weiskirchen R. Clinical features of Wilson disease. Ann Transl Med. 2019;7(Suppl 2):S61. doi:10.21037/atm.2019.01.20
- Xu R, Hajdu CH. Wilson disease and hepatocellular carcinoma. Gastroenterol Hepatol (N Y). 2008;4(6):438-439.
- Wilkinson ML, Portmann B, Williams R. Wilson’s disease and hepatocellular carcinoma: possible protective role of copper. Gut. 1983;24(8):767-771. doi:10.1136/gut.24.8.767
- Harada M. Wilson disease and hepatocellular carcinoma. Intern Med. 2004;43(11):1012-1013. doi:10.2169/internalmedicine.43.1012
Reviewed by Hasan Avcu, MD, on 10/30/2022.