CALRins5-mediated clonal hematopoiesis causes severe hemolytic anemia in a female PGK1Ser320Asn carrier

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URI: http://hdl.handle.net/10952/9100
DOI: 10.1038/s41408-025-01216-w

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carl mediate clonal.pdf (113.07 KB)

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2025

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Hereditary hemolytic anemias (HHA) are rare inherited red blood cell (RBC) disorders caused by genetic abnormalities (hemoglobino/membrano/enzymopathies), characterized by anemia due to premature RBC destruction and intrinsic RBC defects. One of the rarer enzymopathies involves a deficiency in phosphoglycerate kinase 1 (PGK1), an X-linked gene critical for ATP production via glycolysis [1]. PGK1 mutations causing deficiency (OMIM#300653) [2] follow an X-linked recessive inheritance pattern, affecting hemizygous males, while female carriers are generally asymptomatic or may have mild symptoms -consistent with mosaicism for PGK1 activity-[2]. Despite PGK1 is ubiquitously expressed, its deficiency mainly affects the blood, central nervous system (CNS), and skeletal muscle, resulting in chronic hemolysis -with or without anemia-, neurological disorders, or myopathies [1]. Likely explained by the causative PGK1 mutation [3], hemolytic anemias (HA) tends to co-occur with CNS defects, whereas myopathies are almost exclusively observed [3, 4]. To date, approximately 40 patients harboring 30 different mutations have been reported [5]. This report presents the first case of severe HA in a female PGK1 mutation heterozygous carrier [6], which became apparent coinciding with the diagnosis of essential thrombocythemia (ET); and elucidates the mechanism by which a clonal disorder transforms a germline recessive disease into a tissue-specific dominant condition.

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Medicina

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journal article

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Morales, M.L., Cano, H., de la Morena-Barrio, B. et al. CALRins5-mediated clonal hematopoiesis causes severe hemolytic anemia in a female PGK1Ser320Asn carrier. Blood Cancer J. 15, 8 (2025). https://doi.org/10.1038/s41408-025-01216-w

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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