Wilson's disease: a challenging diagnosis. Clinical manifestations and diagnostic procedures in 12 patients

Wilson disease is a neurodegenerative disease of copper metabolism. The genetic defect, localized to chromosome arm 13q, has been shown to affect the copper-transporting adenosine triphosphatase (ATPase) gene (ATP7B) in the liver. Our aim was to study the clinical and laboratory characteristics of 12 children and young adults diagnosed with WD and point out the diagnostic difficulties.

We retrospectively analyzed the patients diagnosed with Wilson's disease between 2001 and 2009 diagnosed in Constanţa County Emergency Hospital. Evaluation included detailed physical examination, conventional laboratory testing, genetic analysis, and liver biopsy.

Patients with hepatic symptoms showed a considerably earlier onset of symptoms and a shorter diagnostic delay before definitive diagnosis than those with neuropsychiatrical symptoms. The mean age at diagnosis was 9.12 +/- 2.59 years (range 5 years-20 years). 10 patients were symptomatic, 6 were referred because of abnormal liver function test results and/or hepatomegaly, 4 had neuropsychiatrical symptoms and 2 received their diagnoses after family screening. Hepatic copper concentration was between 250 and 1200 micrograms/g. 4 patients had liver cirrhosis, five chronic hepatitis and one had massive hepatic necrosis on necropsy. Any person with recurrent hepatic disease and unexplained neurological symptoms should be investigated to have Wilson's disease.

Detection of WD in children and young adults remains very difficult. The most important investigation is liver biopsy with the assessment of liver copper. Genetic analysis may help in doubtful cases.