[Identification of genetically determined chronic childhood cytopenia in the era of molecular medicine].

Abstract

The vast majority of childhood cytopenias are transient, mostly secondary, and not the consequence of primary bone marrow processes. Yet, every few months we see patients in the pediatric hematology centers of the Hungarian Pediatric Oncology Network in whom repeated bone marrow sampling and extensive laboratory hematological investigations do not lead to a diagnosis and the cytopenia persists chronically. In these cases, the identification or exclusion of genetically determined benign or premalignant hematological conditions – such as congenital neutropenia, hereditary hemolytic or dyserythropoietic anemia, inherited thrombocytopenia, congenital bone marrow failure syndrome – is essential for modern therapy planning. In correctly selected pediatric patients with chronic cytopenia, modern high-throughput molecular genetic testing by next-generation sequencing is the most cost-effective diagnostic option, and its early use avoids many invasive interventions and inappropriate therapeutic attempts. At the initiative of Semmelweis University, a national molecular genetic diagnostics program was launched to map the etiology, epidemiology and prognosis of hereditary chronic cytopenias in children in Hungary. In the present work, we summarize the technical details of the testing modality and the indications we propose to apply in clinical practice. As a proof of concept, we present a discovery cohort of 30 patients selected according to these indications: 67% of them were identified with a gene variation that at least partially explained the phenotype, 47% with a variation that revised the diagnosis initially assumed by the treating physician, and 43% with a variation that determined the next substantive therapeutic decision. Of these, 45% were likely pathogenic or pathogenic aberrations and 55% were variants of unknown clinical significance. We propose to consider and apply this high-throughput molecular genetic modality, which generates significant clinical benefit and has a high diagnostic success rate according to our own and international data presented, as a priority element of the hematological diagnostic workflow in our country, within a regulated, professional framework. Orv Hetil. 2025; 166(1): 3–19.