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

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 ].