New analytical approaches for copper diagnosis, prognosis and follow up of wilson disease
- Autores: M. Carmen García Poyo
- Directores de la Tesis: Christophe Pecheyran (dir. tes.), Martín Resano Ezcaray (dir. tes.)
- Lectura: En la Universidad de Zaragoza ( España ) en 2021
- Idioma: español
- Materias:
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- Resumen
Copper is an essential metal involved in many metabolic reactions. In particular, it is linked to Wilson's disease (WD) caused by a mutation of the ATP7B gene which leads to an accumulation of copper in the organs (livers, brains, kidneys, eyes, etc.). This disease can be fatal if left untreated. Although the treatment is relatively simple and effective, the problem is to be able to diagnose the disease early enough, before the symptoms appear.
Usually, biomonitoring is carried out using blood samples taken by venipuncture. However, in order to compensate for this relatively invasive method (especially for newborns) and which generally requires a trip to a medical analysis laboratory, new micro-sampling devices allowing only a few microlitres to be taken, initially developed for the monitoring of biomarkers (antibodies, DNA, protein, etc.) were used in this thesis.
In this context, different analytical methods have been developed in the framework of this thesis for the elemental determination of copper and its isotopic composition, based on micro-sampling techniques.
In particular, two methods have been developed and evaluated for the elemental analysis of copper. The first one, dedicated to the direct analysis of solids by HR CS GFAAS, allowed the evaluation of different dried blood spot sampling device. A new interference correction algorithm based on the time resolved absorbance profile (TAP) was developed and applied to the analysis of liquid and solid samples. The second method was applied to the analysis of liquid samples by ICP-MS using only 1 µl of sample.
Three methods were also developed and evaluated for the isotopic analysis of copper, the first using a femtosecond laser, the second using Electro Thermal Vaporisation (ETV) and the last using direct liquid micro-injection.
These methods were used to study the diagnosis, prognosis and follow-up of Wilson's disease.
Finally, it was observed that relative exchangeable copper (REC) seems to be a good parameter to differentiate Wilson's disease patients from other groups. The other parameters, especially copper isotopic composition, can be used for the follow-up of the disease.
