<br>        Inclusion Criteria:<br><br>          -  Informed consent;<br><br>          -  Male or female, aged 18 years or older;<br><br>          -  Documented clinical laboratory confirmation of pyruvate kinase deficiency (PKD),<br>             defined as documented presence of at least 2 mutant alleles in the PKLR gene, of which<br>             at least 1 is a missense mutation;<br><br>          -  Hb concentration less than or equal to 10.0 g/dL regardless of gender (average of at<br>             least 2 Hb measurements [separated by a minimum of 7 days] during the Screening<br>             Period)<br><br>          -  Considered not regularly transfused, defined as having had no more than 4 transfusion<br>             episodes in the 12-month period up to the first day of study treatment and no<br>             transfusions in the 3 months prior to the first day of study treatment;<br><br>          -  Received at least 0.8 mg oral folic acid daily for at least 21 days prior to the first<br>             dose of study treatment, to be continued daily during study participation.<br><br>          -  Adequate organ function;<br><br>          -  Women of reproductive potential, have a negative serum pregnancy test;<br><br>          -  For women of reproductive potential as well as men with partners who are women of<br>             reproductive potential, be abstinent as part of their usual lifestyle, or agree to use<br>             2 forms of contraception, 1 of which must be considered highly effective, from the<br>             time of giving informed consent, during the study, and for 28 days following the last<br>             dose of study treatment for women and 90 days for men following the last dose of study<br>             treatment;<br><br>          -  Willing to comply with all study procedures for the duration of the study;<br><br>        Exclusion Criteria:<br><br>          -  Homozygous for the R479H mutation or have 2 non-missense mutations, without the<br>             presence of another missense mutation, in the PKLR gene;<br><br>          -  Significant medical condition that confers an unacceptable risk to participating in<br>             the study, and/or that could confound the interpretation of the study data;<br><br>          -  Splenectomy scheduled during the study treatment period or have undergone splenectomy<br>             within 12 months prior to signing informed consent;<br><br>          -  Currently enrolled in another therapeutic clinical trial involving ongoing therapy<br>             with any investigational or marketed product or placebo. Prior and subsequent<br>             participation in the PK Deficiency Natural History Study (NHS) (NCT02053480) or PK<br>             Deficiency Registry is permitted however, concurrent participation is not;<br>             participants enrolling in this current study will be expected to temporarily suspend<br>             participation in the NHS or Registry;<br><br>          -  Exposure to any investigational drug, device, or procedure within 3 months prior to<br>             the first dose of study treatment;<br><br>          -  Prior treatment with a pyruvate kinase activator;<br><br>          -  Prior bone marrow or stem cell transplant;<br><br>          -  Currently pregnant or breastfeeding;<br><br>          -  History of major surgery within 6 months of signing informed consent;<br><br>          -  Currently receiving medications that are strong inhibitors of cytochrome P450<br>             (CYP)3A4, strong inducers of CYP3A4, strong inhibitors of P-glycoprotein (P-gp), or<br>             digoxin (a P-gp sensitive substrate medication) that have not been stopped for a<br>             duration of at least 5 days or a timeframe equivalent to 5 half-lives (whichever is<br>             longer) prior to the first dose of study treatment;<br><br>          -  Currently receiving hematopoietic stimulating agents that have not been stopped for a<br>             duration of at least 28 days prior to the first dose of study treatment;<br><br>          -  History of allergy to sulfonamides if characterized by acute hemolytic anemia, drug<br>             induced liver injury, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson<br>             syndrome, cholestatic hepatitis, or other serious clinical manifestations;<br><br>          -  History of allergy to AG-348 or its excipients;<br><br>          -  Currently receiving anabolic steroids, including testosterone preparations, within 28<br>             days prior to treatment.<br>