Tests for Wilson Disease in Asymptomatic Children

Measuring serum ceruloplasmin concentration was confirmed as an adequate initial diagnostic test.

Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism that can lead to liver disease and adverse effects on kidneys, bones, and the nervous system. Early diagnosis and treatment can prevent substantial morbidity but can be challenging, particularly in children.

To evaluate the performance of conventional tests and a recently proposed scoring system for diagnosing WD (Liver Int 2003; 23:139), researchers in Italy studied asymptomatic children with WD — confirmed by an abnormal liver copper concentration plus the identification of two disease-causing mutations or homozygosity for a single disease-causing mutation (the gold standard for diagnosing WD). The diagnostic tests that were assessed measured serum ceruloplasmin level, basal 24-hour urinary copper level, and 24-hour urinary copper level after the penicillamine challenge test (PCT). The WD scoring system measured serum ceruloplasmin level, liver copper level (Rhodanine stain if copper level test was not performed), and 24-hour urinary copper level. Receiver operating characteristic (ROC) analysis measured the sensitivity and specificity of each test at different cutoff values.

Researchers enrolled 40 patients with WD (median age, 6.1 years; 26 males and 14 females) and 58 sex- and age-matched controls with liver disease other than WD. For the serum ceruloplasmin test, a cutoff value of 20 mg/dL achieved sensitivity of 95.0% and specificity of 84.5%. For the basal urinary copper test, a cutoff value of 40 µg/24 hours achieved sensitivity of 78.9% and specificity of 87.9%. The 24-hour urinary copper test after PCT demonstrated poor performance. The WD scoring system had positive and negative predictive values of 93.0% and 91.6%, respectively.

Comment: These findings confirm that serum ceruloplasmin level (<20 mg/dL) is adequate as an initial diagnostic test for WD in children with asymptomatic disease. The 24-hour urine copper test is not as good, and the 24-hour urinary copper test after PCT is poor. The WD scoring system has excellent diagnostic characteristics but requires a liver biopsy. Therefore, clinicians should be confident about using serum ceruloplasmin level as the initial test. If the level is normal, then no further work-up is required. However, if the level is low, clinicians should proceed with a liver biopsy and employ the WD scoring system.

Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology February 11, 2011

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