Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson's disease in children.
OBJECTIVE
A urinary copper (Cu) >25 micromol/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.


METHODS
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 24h before (basal Cu) and for 24h whilst giving penicillamine 500 mg orally 12 hourly x 2 (post-penicillamine Cu).


RESULTS
Both basal Cu and post-penicillamine Cu differed significantly between WD patients and controls (basal Cu: median 6.5 micromol/24 h, range 0.9-109 micromol/24 h, versus median: 0.8 micromol/24 h, range 0.1-19.5, p<0.0001; post-penicillamine Cu: median 36.9 micromol/24 h, range 1.98-219 micromol/24 h, versus median 12.35 micromol/24 h, range 0.5-49.8 micromol/24 h, p<0.0001). A post-penicillamine Cu >25 micromol/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%]).


CONCLUSIONS
This test is valuable in the diagnosis of WD with active liver disease, but is unreliable to exclude the diagnosis in asymptomatic siblings.
Müller
Thomas
T
Department of Pediatrics II, Medical University of Innsbruck, Innsbruck, Austria.
Koppikar
Smita
S
Taylor
Rachel M
RM
Carragher
Fiona
F
Schlenck
Barbara
B
Heinz-Erian
Peter
P
Kronenberg
Florian
F
Ferenci
Peter
P
Tanner
Stuart
S
Siebert
Uwe
U
Staudinger
Roland
R
Mieli-Vergani
Giorgina
G
Dhawan
Anil
A
D000293:Adolescent; D002570:Ceruloplasmin / Q000378:metabolism; D002614:Chelating Agents; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm; D003300:Copper / Q000097:blood / Q000378:metabolism / Q000652:urine; D004252:DNA Mutational Analysis; D003938:Diagnostic Techniques, Digestive System / Q000592:standards*; D005260:Female; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D010396:Penicillamine; D012680:Sensitivity and Specificity
D002614:Chelating Agents; D003300:Copper; D002570:Ceruloplasmin; D010396:Penicillamine