CLINICAL LABORATORY AND MOLECULAR GENETIC DIAGNOSIS OF WILSON-KONOVALOV DISEASE

Introduction. The clinical picture of Wilson-Konovalov disease (WKD) is characterized by pronounced polymorphism and classical laboratory findings often do not allow to make diagnosis. The most reliable way to confirm the presence of WKD is to identify mutations in the ATP7B gene. Materials and methods. In the course of the research, we developed a method of genetic diagnostics, including realtime PCR to determine a point mutation in combination with fragment analysis to identify deletions and insertions. 20 patients were collected in whom the diagnosis of WKD was made basing on the results of clinical and laboratory criteria of the disease according to the Leipzig scoring system. All patients were genotyped with the developed technique. Anamnestic, clinical, and laboratory data were collected for 12 patients. Results. We detected the following aberrancies in patients from the group 1: heterozygous mutations according to H1069Q (60%), homozygous mutations according to H1069Q (30%), combination of mutations 3627_3630del.4/ H1069Q in heterozygous form (5%), combination of mutations1770insT/H1069Q in heterozygous form (5%). Discussion. Clinical feature of WKD is non-specific, and the combination of liver and nervous system damage typical for WKD, Kayser–Fleischer rings are far from being present in all patients or appear in the later stages of the disease. A considerable amount of false-negative results of WKD laboratory markers indicates the insufficient sensitivity of these research methods. The variability of clinical and laboratory markers of WKD delays the etiology diagnosis and the onset of pathogenetic therapy. Conclusion. The developed method of genetic diagnosis of WKD is recommended for all patients of the Russian population with suspected hepatic, neurological or mixed form of WKD in order to make a timely diagnosis and start treatment.