What are the symptoms and treatment options for children with Wilson disease?

Wilson Disease in Children: Symptoms and Treatment

Children with Wilson disease primarily present with liver disease, which can range from asymptomatic hepatomegaly to acute liver failure, while neuropsychiatric manifestations are less common but include declining school performance, personality changes, and movement disorders. 1

Clinical Presentations in Children

Liver Manifestations

• Asymptomatic hepatomegaly - Often the earliest finding in children
• Elevated liver enzymes - May be the only initial abnormality
• Variable liver disease presentations:
  • Asymptomatic with only biochemical abnormalities
  • Acute hepatitis resembling viral infection
  • Chronic hepatitis
  • Cirrhosis (compensated or decompensated)
  • Acute liver failure (may be associated with Coombs-negative hemolytic anemia)
  • May resemble autoimmune hepatitis 1

Neuropsychiatric Manifestations

• Generally less common in children compared to adults but can include:
  • Behavioral changes: declining school performance, personality changes
  • Psychiatric symptoms: impulsiveness, labile mood, inappropriate behavior 1
  • Movement disorders:
    • Deterioration in handwriting (micrographia)
    • Tremor (especially "wing-beating" tremor)
    • Dysarthria and speech changes
    • Drooling (often an early neurologic symptom)
    • Dystonia 1

Other Manifestations

• Kayser-Fleischer rings - Golden-brownish pigment in cornea (may be absent in children with only liver disease)
• Hemolytic anemia - May occur with or without liver disease
• Renal abnormalities - Aminoaciduria and nephrolithiasis
• Skeletal abnormalities - Premature osteoporosis and arthritis 1

Diagnostic Approach

1. Laboratory tests:

   • Serum ceruloplasmin (typically < 20 mg/dL)
   • Liver function tests (elevated aminotransferases)
   • 24-hour urinary copper excretion (may be normal in children under 6 years) 2
   • Complete blood count (to detect hemolysis)

2. Ophthalmologic examination:

   • Slit-lamp examination for Kayser-Fleischer rings

3. Liver biopsy:

   • Quantitative hepatic copper content (>250 mcg/g dry weight is diagnostic) 3
   • Particularly important when other tests are inconclusive

4. Genetic testing:

   • ATP7B gene mutations analysis 1

Treatment Options

Medical Treatment

1. Copper chelation therapy:

   • D-penicillamine - First-line treatment 3

     • Promotes urinary excretion of copper
     • Dosage for children with Wilson disease should be carefully monitored
     • Neurological symptoms may worsen temporarily during initial therapy
     • Side effects require monitoring (proteinuria, hematologic abnormalities)

   • Trientine - Alternative for patients who cannot tolerate penicillamine 3

2. Zinc therapy:

   • Blocks intestinal absorption of copper
   • May be preferred for presymptomatic children 4
   • Generally has fewer side effects than chelators

3. Dietary modifications:

   • Low-copper diet (avoid chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli)
   • Use distilled or demineralized water if drinking water contains >0.1 mg/L copper 3

Monitoring

• Liver function tests every 3 months during first year of treatment 3
• Regular assessment of urinary copper excretion
• Regular neurological evaluations
• Annual ophthalmologic examination for Kayser-Fleischer rings

Liver Transplantation

• Reserved for severe cases:
  • Fulminant hepatic failure unresponsive to medical therapy
  • Decompensated cirrhosis
  • Severe neurological disease unresponsive to medical therapy 1

Prognosis

• Untreated: Universally fatal
• With treatment:
  • Liver function typically normalizes within 1-2 years in patients without or with compensated cirrhosis
  • Neurological symptoms may improve but are often only partially reversible
  • Early diagnosis and treatment (especially in presymptomatic children) leads to near-normal longevity 4
  • Lifelong treatment adherence is essential 1

Important Considerations and Pitfalls

1. Don't miss Wilson disease in children with apparent autoimmune hepatitis - All children with suspected autoimmune hepatitis should be evaluated for Wilson disease 1

2. Age of presentation can be younger than expected - The youngest reported patient with cirrhosis due to Wilson disease was 3 years old 1

3. Normal ceruloplasmin doesn't rule out Wilson disease - Up to 14% of children with Wilson disease may have normal ceruloplasmin levels 2

4. Family screening is essential - First-degree relatives of any patient newly diagnosed with Wilson disease must be screened 1

5. Treatment interruption risks - Once started, treatment should be continued daily without interruption, as breaks can lead to sensitivity reactions upon resumption 3

6. Neurological worsening during treatment initiation - Temporary neurological deterioration may occur when starting penicillamine but is not a reason to discontinue therapy 3