Wilson's Disease Symptoms

Key Takeaways

• Early clues are usually vague: fatigue, nausea, abdominal pain and unexplained drops in school performance or mood.

• Liver-related signs: jaundice, raised liver enzymes, hepatosplenomegaly, itching (pruritus) and possible progression to cirrhosis.

• Neurologic features: tremor, rigidity, ataxia, dysarthria and movement problems from copper buildup in the basal ganglia.

• Psychiatric changes can include depression, anxiety, personality shifts and cognitive decline that sometimes appear before movement symptoms.

• Kayser‑Fleischer rings on slit‑lamp exam and systemic findings (hemolysis, renal tubular dysfunction) help confirm the diagnosis.

What Causes Copper Buildup in Wilson’s Disease?

How does copper accumulate in Wilson’s disease? The condition stems from mutations in ATP7B, a key copper transporter in liver cells, and is inherited in an autosomal recessive pattern. Defective ATP7B reduces incorporation of copper into ceruloplasmin and impairs biliary copper excretion, causing hepatic copper accumulation. When the liver can no longer store excess copper, it spills into the bloodstream and deposits in other organs, producing systemic copper buildup. Normal cellular copper handling involves CTR1 uptake and ATOX1 delivery to ATP7B; when ATP7B function falls, free intracellular copper rises and generates reactive oxygen species. The resulting oxidative damage mainly affects the liver, brain (especially the basal ganglia), kidneys and eyes. Low ceruloplasmin levels reflect this disrupted copper handling.

Early Warning Signs and General Symptoms

When do symptoms typically appear? Wilson’s disease most often becomes noticeable in childhood or adolescence (roughly ages 6–20). Early warning signs are nonspecific: fatigue, nausea, abdominal pain and subtle changes in mood or school performance. Liver symptoms may be the first sign or can occur alongside neuropsychiatric issues such as mood shifts, anxiety and memory problems. Tremor, stiffness and speech difficulties point to neurological involvement. Kayser‑Fleischer rings on eye exam often accompany neurologic signs. Early evaluation helps limit further damage.

Liver-Related Symptoms and Complications

Liver involvement in Wilson disease usually shows as hepatic injury and reduced liver function: fatigue, jaundice, pruritus, nausea, vomiting and peripheral edema; hemolysis can worsen jaundice. Progressive copper overload in hepatocytes causes inflammation and cell death, producing abnormal liver enzymes on blood tests. Early liver signs may include right‑upper‑quadrant discomfort and abnormal labs; without treatment the disease can lead to hepatosplenomegaly and portal hypertension. Chronically, this damage may progress to cirrhosis with synthetic failure, coagulopathy, ascites and higher infection risk. In advanced cases, decompensation can lead to liver failure, which may be fatal without transplantation. Timely diagnosis and copper‑chelating treatment aim to prevent these outcomes and protect liver function.

Neurological and Psychiatric Manifestations

After liver involvement, copper can accumulate in the central nervous system and produce a range of neurological and psychiatric signs. Copper deposition in the basal ganglia commonly causes tremor, rigidity, ataxia and clumsiness. Speech is often affected — hypophonia and dysarthria are common and can increase swallowing and aspiration risk. Neuropsychiatric features affect roughly 30–50% of patients and include mood changes, anxiety, personality shifts and cognitive decline. Kayser‑Fleischer rings frequently accompany neurologic presentations and support the diagnosis. Early recognition of movement and behavioral changes is important so treatment can limit irreversible harm.

Eye Findings and Other Systemic Effects

How does copper deposition show up outside the liver and brain? Kayser‑Fleischer rings are a classic ocular sign: a rusty brown corneal rim visible on slit‑lamp exam, often seen with neurologic symptoms. Copper overload also causes wider systemic effects: hepatic involvement ranges from fatigue and jaundice to edema, ascites and cirrhosis as disease progresses. Neurological manifestations can worsen to tremor, dysarthria, hypophonia, ataxia and abnormal gait, alongside personality changes, mood disorders and cognitive decline. Kidneys may be affected through tubular dysfunction, which can cause hematuria and other abnormalities. These multisystem signs underscore the need to recognize eye findings and other organ effects so evaluation and treatment can start before damage becomes irreversible.