What are the symptoms of Wilson's disease?

Symptoms of Wilson's Disease

Wilson's disease presents with a wide spectrum of hepatic, neurological, psychiatric, and other systemic manifestations due to copper accumulation in various organs, primarily affecting the liver and brain. 1

Hepatic Manifestations

Wilson's disease commonly presents with liver symptoms, which may include:

• Jaundice, anorexia, and vomiting (14-44% of patients)
• Ascites and edema (14-50% of patients)
• Hepatomegaly and splenomegaly (15-49% of patients)
• Acute liver failure (up to 17% of patients)
• Variceal hemorrhage (3-10% of patients)
• Hemolysis (5-20% of patients) 1

Liver disease presentations can range from:

• Asymptomatic liver enzyme elevation
• Chronic hepatitis with vague abdominal complaints
• Compensated or decompensated cirrhosis
• Acute liver failure (more common in young females with 4:1 female-to-male ratio) 1

Neurological Manifestations

Neurological symptoms may appear simultaneously with hepatic signs or years later, and can be classified into four main categories:

1. Akinetic-rigid syndrome (similar to Parkinson's disease)
2. Pseudosclerosis dominated by tremor (characteristic "wing beating" tremor)
3. Ataxia
4. Dystonic syndrome 1, 2

Common neurological symptoms include:

• Dysarthria (speech changes, often an early symptom)
• Drooling (often an early symptom)
• Dystonia (can be focal, segmental, or severe)
• Facial grimacing
• Open jaw and lip retraction
• Tremor (coarse, irregular proximal tremulousness) 1

Progressive neurological deterioration can lead to severe disability, with patients becoming bedridden and unable to care for themselves while remaining alert but unable to communicate. 1

Psychiatric Manifestations

About one-third of patients initially present with psychiatric abnormalities:

• In children: declining school performance, personality changes, impulsiveness, labile mood, sexual exhibitionism, and inappropriate behavior
• In adults: psychotic features resembling paranoia, schizophrenia, or depression
• Behavioral changes are common across age groups 1

These symptoms are often misdiagnosed as behavioral problems associated with puberty in children or as primary psychiatric disorders in adults, leading to diagnostic delays (up to 12 years in some cases). 1

Other Clinical Manifestations

Less common presentations include:

• Hemolytic anemia (Coombs-negative)
• Renal abnormalities (aminoaciduria, nephrolithiasis)
• Hypercalciuria and nephrocalcinosis
• Cardiomyopathy
• Myopathy
• Chondrocalcinosis and osteoarthritis
• Hypoparathyroidism
• Pancreatitis
• Infertility or repeated miscarriages 1

Ocular Signs

• Kayser-Fleischer rings - characteristic golden-brown rings in the corneas, present in all patients with cerebral symptoms and some with only hepatic manifestations 3

Clinical Pitfalls and Diagnostic Challenges

1. Diagnostic delays are common, especially in patients with neuropsychiatric presentations 1

2. Neurological symptoms may worsen temporarily during initiation of therapy with penicillamine 3

3. Misdiagnosis is common as symptoms can mimic:

   • Behavioral problems of puberty
   • Primary psychiatric disorders
   • Hepatic encephalopathy in patients with advanced liver disease
   • HELLP syndrome during pregnancy 1, 4

4. No pathognomonic features exist aside from markedly altered copper metabolism, making Wilson's disease difficult to distinguish from more common liver diseases 4

5. Asymptomatic disease can be present in 5-23% of patients with liver involvement, detected only through family screening or routine laboratory testing 1

Early diagnosis and treatment are critical as untreated Wilson's disease is universally fatal, but with proper treatment, the prognosis is excellent, especially for those without cirrhosis at the time of diagnosis. 1, 5