Rapid and reliable diagnosis of Wilson disease using X-ray fluorescence Academic Article uri icon


  • Wilson's disease (WD) is a rare autosomal recessive disease due to mutations of the gene encoding the copper-transporter ATP7B. The diagnosis is hampered by the variability of symptoms induced by copper accumulation, the inconstancy of the pathognomonic signs and the absence of a reliable diagnostic test. We investigated the diagnostic potential of X-ray fluorescence (XRF) that allows quantitative analysis of multiple elements. Studies were performed on animal models using Wistar rats (n = 10) and Long Evans Cinnamon (LEC) rats (n = 11), and on human samples including normal livers (n = 10), alcohol cirrhosis (n = 8), haemochromatosis (n = 10), cholestasis (n = 6) and WD (n = 22). XRF experiments were first performed using synchrotron radiation to address the elemental composition at the cellular level. High-resolution mapping of tissue sections allowed measurement of the intensity and the distribution of copper, iron and zinc while preserving the morphology. Investigations were further conducted using a laboratory X-ray source for irradiating whole pieces of tissue. The sensitivity of XRF was highlighted by the discrimination of LEC rats from wild type even under a regimen using copper deficient food. XRF on whole formalin-fixed paraffin embedded needle biopsies allowed profiling of the elements in a few minutes. The intensity of copper related to iron and zinc significantly discriminated WD from other genetic or chronic liver diseases with 97.6% specificity and 100% sensitivity. This study established a definite diagnosis of Wilson's disease based on XRF. This rapid and versatile method can be easily implemented in a clinical setting.


  • Kaščáková, Slávka
  • Kewish, Cameron M
  • Rouzière, Stéphan
  • Schmitt, Françoise
  • Sobesky, Rodolphe
  • Poupon, Joël
  • Sandt, Christophe
  • Francou, Bruno
  • Somogyi, Andrea
  • Samuel, Didier
  • Jacquemin, Emmanuel
  • Dubart-Kupperschmitt, Anne
  • Nguyen, Tuan Huy
  • Bazin, Dominique
  • Duclos-Vallée, Jean-Charles
  • Guettier, Catherine
  • Le Naour, François

publication date

  • 2016