Diagnostic Value of Ceruloplasmin in the Diagnosis of PediatricWilson’s Disease
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: Measurement of serum ceruloplasmin level is the first step in screening for Wilson's disease (WD). Despite the rarity of WD in the general population, ceruloplasmin levels are routinely measured through hepatitis screening in both adults and children. Herein, we evaluated the diagnostic value of ceruloplasmin for the diagnosis of WD among children with hepatitis.Methods: We retrospectively reviewed data on serum ceruloplasmin levels measured as a serologic marker for pa-tients with hepatitis at Asan Medical Center (Seoul, Korea) between from January 2004 to November 2013. The diagnosis of WD was confirmed by the identification of pathogenic variants in the ATP7B gene. To determine the diagnostic accuracy of ceruloplasmin, receiver operation characteristic (ROC) curves were constructed and the area under curve (AUC) were calculated. Results: Measurements of serum ceruloplasmin were performed in 2,834 children who had hepatitis. Among these, 181 (6.4%) children were diagnosed with WD. The sensitivity, specificity, and accuracy of a ceruloplasmin level of ＜20 mg/dL in the discrimination of WD were 93.4%, 84.2%, and 84.8%, respectively. In this study, 418 (14.7%) false-positive cases and 12 (0.4%) false-negative cases were noted. Using a ROC curve, a ceruloplasmin level of ≤16.6 mg/dL showed the highest AUC value (0.956) with a sensitivity of 91.2%, a specificity of 94.9%, and an accu-racy of 94.7%.Conclusion: The measurement of serum ceruloplasmin was frequently used for the screening of WD in children, despite a low positive rate. The diagnostic value of ceruloplasmin may be strengthened by adopting a new lower cut-off level.
Abstract
Purpose: Measurement of serum ceruloplasmin level is the first step in screening for Wilson's disease (WD). Despite the rarity of WD in the general population, ceruloplasmin levels are routinely measured through hepatitis screening in both adults and children. Herein, we evaluated the diagnostic value of ceruloplasmin for the diagnosis of WD among children with hepatitis.Methods: We retrospectively reviewed data on serum ceruloplasmin levels measured as a serologic marker for pa-tients with hepatitis at Asan Medical Center (Seoul, Korea) between from January 2004 to November 2013. The diagnosis of WD was confirmed by the identification of pathogenic variants in the ATP7B gene. To determine the diagnostic accuracy of ceruloplasmin, receiver operation characteristic (ROC) curves were constructed and the area under curve (AUC) were calculated. Results: Measurements of serum ceruloplasmin were performed in 2,834 children who had hepatitis. Among these, 181 (6.4%) children were diagnosed with WD. The sensitivity, specificity, and accuracy of a ceruloplasmin level of ＜20 mg/dL in the discrimination of WD were 93.4%, 84.2%, and 84.8%, respectively. In this study, 418 (14.7%) false-positive cases and 12 (0.4%) false-negative cases were noted. Using a ROC curve, a ceruloplasmin level of ≤16.6 mg/dL showed the highest AUC value (0.956) with a sensitivity of 91.2%, a specificity of 94.9%, and an accu-racy of 94.7%.Conclusion: The measurement of serum ceruloplasmin was frequently used for the screening of WD in children, despite a low positive rate. The diagnostic value of ceruloplasmin may be strengthened by adopting a new lower cut-off level.
참고문헌 (17)
- Litwin T, "Wilson disease-factors affecting clinical presentation", Neurol Neurochir Pol, 47, pp.161~169 (2013)
- Manolaki N, "Wilson disease in children:analysis of 57 cases", J Pediatr Gastroenterol Nutr, 48, pp.72~77 (2009)
- Huster D, "Wilson disease", Best Pract Res Clin Gastroenterol, 24, pp.531~539 (2010)
- Endo F, "Measurement of blood holoceruloplasmin by EIA using a mouse monoclonal antibody directed to holoceruloplasmin. Implication for mass screening of Wilson disease", J Inherit Metab Dis, 17, pp.616~620 (1994)
- Ohura T, "Pilot study of screening for Wilson disease using dried blood spots obtained from children seen at outpatient clinics", J Inherit Metab Dis, 22, pp.74~80 (1999)
- Yamaguchi Y, "Mass screening for Wilson's disease:results and recommendations", Pediatr Int, 41, pp.405~408 (1999)
- Jeong Kee Seo, "Diagnosis of Wilson Disease in Young Children: Molecular Genetic Testing and a Paradigm Shift from the Laboratory Diagnosis", Pediatric Gastroenterology, Hepatology & Nutrition, 15(4), pp.197~209 (2012), 대한소아소화기영양학회
- Ala A, "Wilson disease in septuagenarian siblings: raising the bar for diagnosis", Hepatology, 41, pp.668~670 (2005)
- Beyersdorff A, "Morbus Wilson: case report of a two-year-old child as first manifestation", Scand J Gastroenterol, 41, pp.496~497 (2006)
- Schoen RE, "Clinical aspects of Wilson's disease", Am J Gastroenterol, 85, pp.1453~1457 (1990)
- Mak CM, "Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects", Clin Chem, 54, pp.1356~1362 (2008)
- Robin X, "pROC: an open-source package for R and S+ to analyze and compare ROC curves", BMC Bioinformatics, 12, pp.77~ (2011)
- Hahn SH., "Population screening for Wilson's disease", Ann N Y Acad Sci, 1315, pp.64~69 (2014)
- Squires RH Jr, "Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group", J Pediatr, 148, pp.652~658 (2006)
- Korman JD, "Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests", Hepatology, 48, pp.1167~1174 (2008)
- Tapper EB, "The overuse of serum ceruloplasmin measurement", Am J Med, 126, pp.e1~5 (2013)
- Ferenci P, "Diagnosis and phenotypic classification of Wilson disease", Liver Int, 23, pp.139~142 (2003)