[Complexity of the diagnosis of Wilson disease in clinical practice: our experience in 15 patients].
BACKGROUND
Wilson disease (WD) is an inherited disorder that causes copper (Cu) accumulation, leading to mainly liver, neurological and/or psychiatric manifestations. In the absence of some of the typical features, diagnosis of WD is difficult and is based on the combination of clinical, biochemical and genetic testing. The aim of this study was to illustrate the complexity of the approach to WD in daily clinical practice.


METHODS
We retrospectively analyzed the medical records of patients with WD, including the clinical presentation, histological and biochemical findings, and follow up after treatment. We also carried out genetic testing, and the Leipzig diagnostic score was applied.


RESULTS
We included 15 patients. Four were symptomatic, with liver (n=1), neurological (n=1), psychiatric (n=1) and mixed clinical manifestations (n=1), and 11 were presymptomatic, with elevated transaminases (n=8) and family study (n=3). We observed Kayser-Fleischer ring in 2 patients, both without neurologic symptoms. Ceruloplasmin ≤ 5 mg/dL was present in 73%, and 24-hour urinary Cu> 100 μg in 40%. Liver Cu was >250 μg/g.d.t. in 85% of the patients. The final diagnosis of WD was given by genetic testing (ATP7B gene mutations) in 5 patients with minimal disease features, including one symptomatic patient (psychiatric symptoms). We identified 5 previously reported mutations (p.M645R, p.R827W, p.H1069Q, p.P768L and p.G869R) and 3 unpublished mutations (p.L1313R, p.I1311T and p.A1179D); the most frequent mutation was p.M645R. After treatment, biochemical parameters (transaminases, urinary cooper) and symptoms improved, except in patients with neurological and psychiatric manifestations.


CONCLUSIONS
Our series illustrates the important role of genetic testing in the diagnosis of WD. The identification of the p.M645R mutation in most of our patients should be kept in mind in the molecular analysis of the ATP7B gene in our region.
Servicio de Aparato Digestivo, Complejo Hospitalario de Navarra, Pamplona, España. Electronic address: phuartem@cfnavarra.es.
María Pilar
MP
Huarte-Muniesa
Servicio de Farmacia, Complejo Hospitalario de Navarra, Pamplona, España.
Esther
E
Lacalle-Fabo
Servicio de Aparato Digestivo, Complejo Hospitalario de Navarra, Pamplona, España.
Juan
J
Uriz-Otano
Servicio de Farmacia, Complejo Hospitalario de Navarra, Pamplona, España.
Silvia
S
Berisa-Prado
Servicio de Genética, Complejo Hospitalario de Navarra, Pamplona, España.
Sira
S
Moreno-Laguna
Servicio de Aparato Digestivo, Complejo Hospitalario de Navarra, Pamplona, España.
María Jesús
MJ
Burusco-Paternáin
D000293:Adolescent; D000328:Adult; D002648:Child; D003955:Diagnostic Tests, Routine; D005260:Female; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
ATP7B gene; Enfermedad de Wilson; Estudio Genético; Gen ATP7B; Genetic testing; Leipzig score; Sales de Cinc; Score de Leipzig; Wilson Disease; Zinc salts