Hematological ABP: Interest of New Generation Sequencing Methods (NGS) to Study Suspicious Fluctuations in Erythropoiesis

We present a case report of an adverse analytical finding (AAF) with suspected doping in an athlete following consumption of a supplement contaminated with Roxadustat, an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIP-PH), which increases erythropoietin production under normoxic conditions. Simultaneously, the athlete biological passport (ABP) profile was reviewed by experts of the World Anti-Doping Agency (WADA) ABP review panel and considered to be atypical and suspect of blood doping. A particular genetic testing was performed, which determined that this athlete had various reasons for fluctuations in her hematological parameters, such as the C677T and 1298C MTHFR mutations leading to chronic folate deficiency which can participate in the development of multiple hormonal and metabolic disturbances, heterozygous missense variant EPAS1 c.1292T>C, p. (Ile431Thr) and a heterozygous missense variant PIEZO1 c.7478T>G, p. (Leu2493Arg), both of which are variants of uncertain significance. This example illustrates the caution required when interpreting an ABP.