Featured ArticleWilson Disease: What Does Copper Have to Do With It?
Section snippets
Pathophysiology
WD is a genetic condition that is inherited when both parents of the affected individual carry 1 copy of the mutated gene, although they are typically asymptomatic. This autosomal recessive inherited pattern is characterized by dysfunction of the ATP7B copper-binding protein in copper transport (identified in 1973), resulting in ineffective excretion of copper into the bile. Copper then accumulates, causing cytotoxicity within the liver and the central nervous system.4,5
Copper, a trace
Clinical Characteristics
WD typically presents as liver disease with hepatic, neurologic, and psychiatric complications. WD must be excluded from any patient with unexplained liver disease and neurologic or neuropsychiatric disorders as well as young patients with an unclear etiology of chronic disease or acute hepatitis.6,8
Diagnosis
Because there is not a singular test that is specific for the diagnosis of WD, a wide variety of tests are performed; however, a combination of findings of low ceruloplasmin levels, Kayser-Fleischer rings, and evidence of neurologic symptoms can be diagnostic for WD. In the case of WD with primary hepatic presentations, Kayser-Fleischer rings may be absent; therefore, it does not rule out WD.8,9
Differential diagnoses to be considered are nonalcoholic fatty liver disease or nonalcoholic
Neurologic Evaluation
The AASLD recommends neurologic evaluation on all patients diagnosed with WD. Before treatment consideration or not long after, a neurologic or movement disorder specialist consultation should be done in patients exhibiting neuropsychiatric issues.
Magnetic resonance imaging of the brain, which is more sensitive than computed tomographic imaging, should be ordered in patients with neurologic symptoms and before initiation of treatment. Imaging always shows abnormalities in patients with
Family Screening
Current society guidelines, including AASLD (2008), EASL (2012), and ESPGHAN (2018) guidelines, recommend familial screening for WD of first-degree relatives.
The AASLD recommends screening of siblings with ATP7B mutation analysis or haplotype studies. When unable to perform genetic testing, they suggest obtaining a complete blood count, an international normalized ratio, a complete metabolic panel, ceruloplasmin, slit lamp examination, and 24-hour urine copper; liver biopsy may also be
Treatment
Better diagnostics of WD has allowed early treatment of asymptomatic patients before progression of disease. Pharmacologic treatment is lifelong; however, in severe disease, LT can be curative. Treatment is tailored to patients with active clinical features as well as those who are asymptomatic.3,4
Symptomatic/active disease treatment is done with chelating agents such as D-penicillamine or trientine (better tolerated); specific chelator treatment is guided by tolerability. Combination therapy
Other Therapies
- 1.
Tetrathiomolybdate, a chelator and a strong decoppering agent, is currently being studied (an international phase 3 study began in 2018), comparing it with standard chelators.3,8
- 2.
Vitamin E or N-acetylcysteine as an adjunctive therapy may offer benefits but needs further studies.8,13
- 3.
Physiotherapy for muscle health8
- 4.
Occupational therapy to promote independence8
- 5.
Speech therapy to assess for aspiration risk and promote and maintain safety8
- 6.
In the setting of decompensated liver disease, active
Special Population: Pregnancy
Both the AASLD and EASL guidelines advocate for modified therapy of WD in pregnancy and the postpartum phase.13 Table 9 outlines the modified treatment guidelines.
Prognosis
Patients with WD have an overall favorable prognosis, even if cirrhotic, as long as they adhere to lifetime therapy. Significant improvement of neurologic complications is seen after starting treatment, usually in 5 to 6 months. However, in patients who portrayed serious neurologic disability when diagnosed, notable disability will most likely become lifelong if it is still evident 2 years after treatment.8
Most improvements in dysphagia and mental health are observed 1 to 2 years into
Human Hepatocyte Transplantation
Allogenic hepatocyte transplantation is another potential therapy in hereditary metabolic liver disease as an alternative to LT due to organ shortage as well as adequate functional allografts. As a response to previous limitations to cell engraftment and selective multiplication of transplanted cells, Barahman et al are looking into using a combination of focal radiation with hepatic cell growth stimuli in order to improve cell engraftment and host liver reproduction of transplanted hepatocytes.
Conclusion
WD presents as abnormal accumulation of copper mainly in the liver, eyes, and brain, which may cause liver disease as well neurologic and psychiatric complications. For advanced practice providers, identification and prompt referral are crucial, as the multidisciplinary approach is essential for the diagnosis and treatment of WD. Anticopper therapies have improved outcomes significantly in this population; favorable prognosis is seen, even in those with cirrhosis as long as they adhere to
Hender Rojas, MSN, ACNP-BC, is a nurse practitioner with the Department of Surgery, Transplant Division, University of Kentucky in Lexington and can be contacted at [email protected].
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Wilson’s disease: a 2017 update
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Hepatocyte transplantation, a step forward?
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Long-term metabolic correction of Wilson’s disease in a murine model by gene therapy
J Hepatol
(2016) Genetics Home Reference, MedlinePlus Genetics
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Diagnosis and treatment of Wilson disease: an update
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Office of Dietary Supplements - Copper
Cited by (0)
Hender Rojas, MSN, ACNP-BC, is a nurse practitioner with the Department of Surgery, Transplant Division, University of Kentucky in Lexington and can be contacted at [email protected].
In compliance with standard ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest.