Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson’s disease in children

• Published in: Journal of hepatology Vol. 47; no. 2; pp. 270 - 276
• Main Authors: Müller, Thomas, Koppikar, Smita, Taylor, Rachel M., Carragher, Fiona, Schlenck, Barbara, Heinz-Erian, Peter, Kronenberg, Florian, Ferenci, Peter, Tanner, Stuart, Siebert, Uwe, Staudinger, Roland, Mieli-Vergani, Giorgina, Dhawan, Anil
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.08.2007; Elsevier
• Subjects: Adolescent; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Ceruloplasmin - metabolism; Chelating Agents; Child; Child, Preschool; Circadian Rhythm; Copper; Copper - blood; Copper - metabolism; Copper - urine; Diagnostic Techniques, Digestive System - standards; DNA Mutational Analysis; Female; Gastroenterology and Hepatology; Hepatolenticular Degeneration - diagnosis; Hepatolenticular Degeneration - genetics; Hepatolenticular Degeneration - metabolism; Hepatolenticular Degeneration - pathology; Humans; Liver; Liver - metabolism; Liver - pathology; Male; Medical sciences; Metabolic diseases; Metals (hemochromatosis...); Other metabolic disorders; Penicillamine; Pharmacology. Drug treatments; Sensitivity and Specificity; Wilson’s disease; PCT; Wilson’s disease; Cu; FHF; Liver; CI; ROC; Penicillamine; KF; Copper; WD; Kayser–Fleischer; Receiver operating characteristic; fulminant hepatic failure; penicillamine challenge test; confidence interval; Human; Performance evaluation; Urine; Nervous system diseases; Wilson disease; Metabolic diseases; Hepatic disease; Enzymopathy; Genetic disease; Sulfur containing aminoacid; Sensitivity; Specificity; Chelating agent; Digestive diseases; Antirheumatic agent; Diagnosis; Child; Wilson's disease
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2007.03.011

A urinary copper (Cu) >25 μmol/24 h following penicillamine had a reported specificity of 98.2% and sensitivity of 88.2% in diagnosing Wilson’s disease (WD). We have re-evaluated this test. Ninety-eight subjects were studied at presentation. Thirty-eight (19 girls, 19 boys; median age 10.3 years; range 5–16 years) had an ultimate diagnosis of WD. Sixty (24 girls, 36 boys; median age 10.1, range 2.3–15 years) had other liver disorders. Urinary Cu was estimated for 24 h before (basal Cu) and for 24 h whilst giving penicillamine 500 mg orally 12 hourly × 2 (post-penicillamine Cu). Both basal Cu and post-penicillamine Cu differed significantly between WD patients and controls (basal Cu: median 6.5 μmol/24 h, range 0.9–109 μmol/24 h, versus median: 0.8 μmol/24 h, range 0.1–19.5, p < 0.0001; post-penicillamine Cu: median 36.9 μmol/24 h, range 1.98–219 μmol/24 h, versus median 12.35 μmol/24 h, range 0.5–49.8 μmol/24 h, p < 0.0001). A post-penicillamine Cu >25 μmol/24 h was observed in 29/38 patients with WD and in 4/60 controls. 25/38 WD patients were symptomatic. Twenty-three of these and 6/13 asymptomatic siblings had a positive test. The test had a sensitivity of 76% (95% confidence interval [CI], 59.8–88.6%) and a specificity of 93% (95% CI, 83.8–98.2%). Sensitivity was better in symptomatic patients (92%, [95% CI; 74–99%]) than asymptomatic (46%, [95% CI; 19.2–74.9%]). This test is valuable in the diagnosis of WD with active liver disease, but is unreliable to exclude the diagnosis in asymptomatic siblings.