Michael Schilsky, MD, is a professor of medicine and medical director of adult liver transplant at Yale-New Haven Transplantation Center.

Michael Schilsky, MD

Challenges and Innovations in Wilson Disease, with Michael Schilsky, MD

, also known as hepatolenticular degeneration, is a genetic disorder of copper metabolism that leads to the accumulation of copper in the liver and other tissues, including the brain.

With an estimated prevalence of 1 case per 30,000 live births in most populations, Wilson disease is rare but serious, with gradual damage from copper accumulation resulting in hepatic, neurologic, and 

 manifestations. With the availability of effective treatment options, early detection and intervention are critical for preventing disease progression, mitigating symptoms, and maintaining quality of life.

, Michael Schilsky, MD, a professor of medicine and medical director of adult liver transplant at Yale-New Haven Transplantation Center, discusses the biggest challenges in Wilson disease and recent innovations that have helped to address some of the field’s largest unmet needs.

Schilsky begins by highlighting the need for tools to effectively monitor patients, citing shortcomings in the historical approach of examining urinary copper excretion. He references novel approaches with better sensitivity, also describing advances in diagnostics that have the potential to be implemented universally and catch the disease during infancy.

However, Schilsky notes that detecting Wilson disease so early introduces questions about when to start treatment. He says the current understanding is that it is relatively safe to wait 2 to 3 years while monitoring copper and diet before slowly initiating therapy.

“Whenever you deal with a rare disorder, and Wilson's disease is typically present in about 1 in 30,000 individuals, the key is really recognizing the disease,” Schilsky said. “If we can have newborn screening, we’ll capture a lot and that would be wonderful. If we don't, we have to continue to raise awareness so that we can identify patients at a younger age before they develop more severe symptoms.”

Schilsky goes on to commend his colleagues working in pediatrics for moving the needle and helping identify more patients at a younger age. He additionally recognizes the work being done by patient organizations that are providing advocacy and support for patients and families.

Considerations for Effectively Managing Wilson Disease, with Michael Schilsky, MD

Editors’ note: Schilsky has relevant disclosures with Vivet Therapeutics, Orphalan, Alexion, Wilson Disease Association, National Institute of Health, DepYmed, and Arbomed.

UpToDate. Wilson disease: Epidemiology and pathogenesis. Jun 19, 2024. Accessed March 24, 2025. 

https://www.uptodate.com/contents/wilson-disease-epidemiology-and-pathogenesis

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Schilsky describes lingering challenges and unmet needs in Wilson disease and highlights recent innovations in monitoring and diagnosis.

With an estimated prevalence of 1 case per 30,000 live births in most populations, Wilson disease is rare but serious, with gradual damage from the accumulation of copper resulting in hepatic, neurologic, and 

 manifestations. With effective treatment options available, early detection and intervention are critical for preventing disease progression, mitigating symptoms, and maintaining quality of life.

, Michael Schilsky, MD, a professor of medicine and medical director of adult liver transplant at Yale-New Haven Transplantation Center, explains the hepatic manifestations of Wilson disease caused by defective copper transport and subsequent excessive copper accumulation in the liver, which, if untreated, can lead to progressive liver damage, cirrhosis, and acute liver failure, as well as neurological deterioration and psychiatric complications.

Schilsky notes that Wilson disease is highly treatable with long-standing established therapies. Specifically, he highlights the role of chelating agents, such as trientine and penicillamine, which accelerate copper excretion, and zinc salts, which reduce intestinal copper absorption.

For patients who are already presenting with symptoms, Schilsky says the goal is to stop these symptoms from progressing and hopefully cause them to regress and improve over time. For those who are diagnosed at an early stage and have not yet developed symptoms, he says with appropriate treatment, these patients may be able to avoid symptoms altogether.

Schilsky emphasizes that the management of Wilson disease extends beyond copper removal, calling attention to the need for ongoing monitoring, dietary modifications, and addressing complications of liver disease such as portal hypertension and hepatocellular carcinoma risk. For patients with neurological symptoms, supportive therapies targeting tremors, dystonia, or psychiatric conditions may be necessary.

While lifelong medical therapy is effective for most patients, Schilsky notes about 5% present with a more severe form of the disease, causing acute liver failure requiring urgent liver transplantation. Ultimately, he stresses that early diagnosis is crucial, as Wilson disease is highly manageable for most patients when detected in its early stages.

UpToDate. Wilson disease: Epidemiology and pathogenesis. Jun 19, 2024. Accessed March 20, 2025. 

Schilsky provides an overview of Wilson disease and describes optimal management strategies, highlighting the importance of early detection and intervention.

Michael Schilsky, MD

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