A 17-year-old boy is brought to the office due to unusual behavior and argumentativeness. He was a pleasant student with good grades until a year ago, when his grades started slipping and he became argumentative with teachers and parents. The patient has a 24-year-old, healthy sister, and family history is unremarkable. He is not sexually active. Temperature is 36.9 C (98.4 F), blood pressure is 112/74 mm Hg, pulse is 78/min, and respirations are 14/min. BMI is 25 kg/m2. Sclerae are anicteric. Mucous membranes are moist. The mouth is held slightly open. The neck is supple. The chest is clear to auscultation. The abdomen is soft and nontender; hepatomegaly is present. There is no splenomegaly or ascites. Neurologic examination shows dysarthria and hyperactive deep tendon reflexes. Which of the following is the best next step in management?
Wilson disease | |
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This adolescent's behavioral changes, neurologic abnormalities, and hepatomegaly are concerning for Wilson disease. This rare, autosomal recessive disease is characterized by abnormal copper deposition in tissues, including the liver, basal ganglia, and corneas.
Young children usually have liver disease, ranging from asymptomatic aminotransferase elevations to hepatomegaly or fulminant hepatic failure. Although liver disease is also present in adolescents and young adults, this age group typically presents with neuropsychiatric disease. Neurologic symptoms may include dysarthria and hyperreflexia, which are seen in this patient. In addition, holding the mouth slightly open due to rigidity can be seen in dystonia or parkinsonism, both of which are neurologic features of Wilson disease. Psychiatric manifestations include academic decline, depression, and irritability.
The diagnosis of Wilson disease is supported by low serum ceruloplasmin, which occurs due to impaired hepatocellular copper transport, leading to decreased ceruloplasmin production. Decreased biliary excretion of copper also leads to increased urinary copper excretion. Additional supportive findings include Coombs-negative hemolytic anemia due to red blood cell copper accumulation and slit-lamp findings of Kayser–Fleischer rings due to corneal copper deposition.
Treatment is lifelong copper chelation therapy (eg, D-penicillamine). In addition, first-degree family members should be screened for Wilson disease mutations.
(Choice A) Although behavioral changes can be associated with seizures, this patient has no tonic-clonic movements or postictal periods, making electroencephalography unnecessary at this time.
(Choice B) Lumbar puncture is indicated for Guillain-Barré syndrome (GBS), characterized by elevated cerebrospinal fluid protein. GBS presents acutely with ascending weakness and hyporeflexia, rather than over time with hyperreflexia, hepatomegaly, and neuropsychiatric disease.
(Choice C) Nerve conduction studies are abnormal in amyotrophic lateral sclerosis, which causes upper (eg, dysarthria) and lower (eg, weakness, atrophy) motor neuron symptoms in adults. Behavioral changes and hepatomegaly would not be present.
(Choice E) Illicit drug use should be considered in any adolescent with behavioral changes and academic decline. However, hepatomegaly in combination with neuropsychiatric changes suggests an infiltrative process such as Wilson disease.
(Choice F) Vitamin B12 deficiency can cause neuropsychiatric symptoms, such as irritability, slowed cognition, dystonia, and dysarthria. However, hyporeflexia is typical, and hepatomegaly would not be seen.
Educational objective:
Wilson disease presents with hepatic, neurologic, and psychiatric symptoms. The diagnosis is supported by low serum ceruloplasmin, increased urinary copper, and Kayser–Fleischer rings on slit-lamp examination.