Nagy Zsófia Flóra, Pfliegler György, Kósa János, Árvai Kristóf, Istenes Ildikó, Doros Attila, Timár Botond, Lakatos Péter, Demeter Judit
Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary.
Centre of Rare Diseases, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Pathol Oncol Res. 2025 Mar 10;31:1612037. doi: 10.3389/pore.2025.1612037. eCollection 2025.
Polycythemia indicates the pathological increase in the number of red blood cells and the rise of hematocrit values. Polyglobulia can be of primary or secondary origin, with the most common primary polycythemia being a myeloproliferative neoplasm, polycythemia vera. Polyglobulia patients may develop cardiovascular complications and thromboembolic events. The gold standard of first-line treatment in polycythemia vera is phlebotomy, which is indicated to keep the hematocrit value below 0.45. Until now the goal to be achieved in secondary polyglobulia has been 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 article 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 completing the usual diagnostic algorithm for polyglobulia no cause could be identified in two of our male patients. Therefore, we set out to perform whole exome sequencing in both patients. Our analysis did not include copy number analysis.
In Patient 1 the p.Ser179Pro variant in the gene was detected in the homozygous state, which is classified as likely pathogenic according to the ACMG guidelines. Homozygous mutations are implicated in Chuvash polycythemia. Segregation analysis was declined by the family. In Patient 2 the gene p.His306Gln variant was detected in the heterozygous form. The gene plays a role in pyruvate metabolism. Family screening did not detect this variant in 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.
红细胞增多症表明红细胞数量病理性增加以及血细胞比容值升高。红细胞增多可分为原发性或继发性，最常见的原发性红细胞增多症是一种骨髓增殖性肿瘤，即真性红细胞增多症。红细胞增多症患者可能会发生心血管并发症和血栓栓塞事件。真性红细胞增多症一线治疗的金标准是放血疗法，目的是使血细胞比容值低于0.45。到目前为止，继发性红细胞增多症的治疗目标与此类似。正如两名患有不同罕见的、由基因决定的红细胞增多症患者的例子所示，在继发性红细胞增多症中，这条经验法则需要重新评估。在我们的文章中，我们介绍了这两名患者的病例，并讨论了应用于患有罕见的、由基因决定的红细胞增多症患者的诊断和治疗原则。
在完成了针对红细胞增多症的常规诊断流程后，我们的两名男性患者均未发现病因。因此，我们对两名患者都进行了全外显子组测序。我们的分析不包括拷贝数分析。
在患者1中，检测到该基因的p.Ser179Pro变异处于纯合状态，根据美国医学遗传学与基因组学学会（ACMG）的指南，该变异被分类为可能致病。纯合突变与楚瓦什红细胞增多症有关。该家族拒绝进行分离分析。在患者2中，检测到该基因的p.His306Gln变异处于杂合形式。该基因在丙酮酸代谢中起作用。家族筛查未在健康家庭成员中检测到该变异。
我们在两名红细胞增多症患者中鉴定出罕见的、可能致病的基因变异，并且由于基因诊断，我们实施了个体化的患者监测。我们建议在不明原因的红细胞增多症病例中采用高通量基因组检测。
