ORIGINAL ARTICLE Usefulness of penicillamine-stimulated urinary copper excretion in the diagnosis of adult Wilson’s disease JOSE ´ RAMO ´ N FORUNY 1 , DANIEL BOIXEDA 1 , ANTONIO LO ´ PEZ-SANROMAN 1 , ENRIQUE VA ´ ZQUEZ-SEQUEIROS 1 , MO ´ NICA VILLAFRUELA 1 , MANUEL VA ´ ZQUEZ-ROMERO 1 , MIGUEL RODRI ´ GUEZ-GANDI ´ A 1 , CARLOS MARTI ´ N DE ARGILA 1 , CRISTINA CAMARERO 2 & JOSE ´ MARI ´ A MILICUA 1 Departments of 1 Gastroenterology, and 2 Pediatrics, Hospital Ramo ´n y Cajal, Madrid, Spain Abstract Objective. Diagnosis of Wilson’s disease (WD) is reliant on liver biopsy (LB) and measurement of hepatic copper. The aim of this study was to determine the usefulness of penicillamine-stimulated urinary copper excretion (PS-UCE), a non- invasive diagnostic test, for the diagnosis of WD in adults. Material and methods. In this prospective study of patients with suspected WD, total serum copper, ceruloplasmin, basal 24-h UCE and PS-UCE levels were measured. LB with copper determination was performed in those patients with persistent hypertransaminasemia and low ceruloplasmin or basal UCE 40 mg/24 h. Diagnosis was established if the ceruloplasmin level was found to be B20 mg/dl and hepatic copper 250 mg/g. Results. A total of 115 patients were studied; LB was performed in 43, and WD was diagnosed in 6 (13.9%). Significant differences between WD and non-WD patients were found for basal UCE (WD: median 134.3 mg/24 h versus non-WD: median 19.0 mg/24 h (p B0.05)) and PS-UCE (WD: median 1284.0 mg/24 h versus non-WD: median 776.0 mg/24 h; p B0.01). In the ROC (receiver-operated curve) analysis, PS-UCE was the best discriminant between WD and non-WD (area under the curve (AUC) 0.911, best cut-off point 1057 mg/24 h, 100% sensitivity, 82.3% specificity). Conclusions. PS-UCE is probably a useful non-invasive test in the diagnosis of WD, improving the selection of patients for diagnostic liver biopsy. Patients with PS-UCE under 1057 mg/24 h only rarely will suffer from WD and are unlikely to benefit from LB. Key Words: Diagnosis, penicillamine, Wilson’s disease Introduction Wilson’s disease (WD) is an autosomal recessive hereditary disorder with a prevalence of 30 cases per million [1]. Despite its rarity, WD has to be considered in the differential diagnosis of any patient with chronic liver disease or fulminant hepatic failure. Early detection allows early specific treatment, which modifies the natural history of the disease. The outcome is bleak if no therapy is applied [2]. The diagnosis of WD with hepatic presentation is reliant on a high index of suspicion, and may prove challenging in the absence of typical extrahepatic manifestations (Kayser-Fleischer (KF) rings or neu- ropsychiatric symptoms). None of the available laboratory diagnostic tests (total serum copper, serum non-ceruloplasmin-bound copper, cerulo- plasmin, or basal 24-h urinary copper excretion) have adequate sensitivity and specificity to provide the diagnosis with certainty in all cases; thus, liver biopsy (LB) is often necessary to assess the hepatic copper concentration [3]. Although many investiga- tors consider hepatic copper content 250 mg/g dry weight to be the most reliable test for diagnosis of WD, it can be normal in up to 18% of WD patients [4,5]; thus the diagnosis of adult WD is a problem that cannot be solved by hepatic copper assay alone. According to Sternlieb [6,7], diagnosis of WD can be based on the presence of at least two of the following findings: a) KF rings, as detected by slit- lamp examination, b) serum ceruloplasmin B20 mg/dl, c) typical neurological symptoms and d) Correspondence: Jose ´ Ramo ´n Foruny, MD, Servicio de Gastroenterologı ´a. Hospital Ramo ´n y Cajal, Cra Colmenar, K9.1. ES-28034 Madrid, Spain. Tel:/Fax: 34 91 3368 355. E-mail: jforuny@yahoo.es Scandinavian Journal of Gastroenterology, 2008; 43: 597603 (Received 12 October 2007; accepted 5 December 2007) ISSN 0036-5521 print/ISSN 1502-7708 online # 2008 Taylor & Francis DOI: 10.1080/00365520701847044