AUTHOR=Nagy Zsófia Flóra , Pfliegler György , Kósa János , Árvai Kristóf , Istenes Ildikó , Doros Attila , Timár Botond , Lakatos Péter , Demeter Judit 

TITLE=Case Report: Importance of high-throughput genetic investigations in the differential diagnosis of unexplained erythrocytosis

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 31 - 2025

YEAR=2025

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2025.1612037

DOI=10.3389/pore.2025.1612037

ISSN=1532-2807

ABSTRACT=Polycythaemia means the pathological elevation of the red blood cell count and the rise of hematocrit values. Polyglobulia might be of primary or of secondary origin, the most common primary polycythaemia is a myeloproliferative neoplasm, polycythaemia vera. Polyglobulic patients might develop cardiovascular complications and thromboembolic events. The gold standard of first line treatment in polycythaemia vera is phlebotomy, it is indicated to keep the hematocrit value below 0.45. Until now the goal to be achieved in secondary polyglobulia was similar. In secondary polyglobulia this rule of thumb needs to be re-evaluated as shown by the example of two patients suffering from different rare, genetically determined polyglobulias. In our paper we present the case of these two patients and discuss the diagnostic and therapeutic principles to be applied in patients with rare, genetically determined polyglobulias.After having completed the usual diagnostic algorithm for polyglobulia no cause could be identified in two our male patients. Therefore, we set out to perform whole exome sequencing on both patients. Our analysis did not include copy number analysis.In Patient 1 the p.Ser179Pro variant in the VHL gene was revealed in a homozygous state, which is classified as likely pathogenic according to the ACMG guidelines. Homozygous VHL mutations are implicated in Chuvash polycythaemia. Segregation analysis was refused by the family.In Patient 2 the PKLR gene p.His306Gln variant was detected in heterozygous form. The gene plays a role in pyruvate metabolism. Family screening did not detect this variant in the healthy family members.We identified rare, possibly pathogenic genetic variants in two patients with polyglobulia and as a consequence of the genetic diagnosis we implemented individualized patient monitoring.We recommend the utilization of high-throughput genomic testing in cases with unexplained polyglobulia.