Pyruvate Kinase Deficiency Clinical Trials 2026 — Find Recruiting Studies

About Pyruvate Kinase Deficiency

Pyruvate kinase deficiency is the most common hereditary red cell glycolytic enzymopathy, caused by biallelic mutations in the PKLR gene encoding red blood cell pyruvate kinase, an enzyme critical for ATP generation in erythrocytes via the Embden-Meyerhof glycolytic pathway. Reduced ATP production leads to impaired red cell membrane integrity, premature splenic sequestration and destruction, and chronic non-spherocytic hemolytic anemia of variable severity. Severity ranges from mild compensated hemolysis to transfusion-dependent anemia requiring splenectomy or, in severe cases, hematopoietic stem cell transplantation, with the first oral PK activator (mitapivat) approved in 2022.

Common Clinical Features

Chronic non-spherocytic hemolytic anemia Neonatal jaundice often requiring phototherapy or exchange transfusion Splenomegaly from splenic sequestration Pallor and chronic fatigue Cholelithiasis from chronic hemolysis and bilirubin gallstones Growth retardation in severe childhood cases Iron overload from transfusions and increased gastrointestinal absorption Paradoxical reticulocytosis post-splenectomy

Clinical Trial Eligibility Tips

What to know before applying to Pyruvate Kinase Deficiency trials.

Molecular confirmation of biallelic PKLR mutations and baseline pyruvate kinase enzyme activity assay in red cells are essential for trial enrollment; results must typically be obtained from a reference laboratory.

Transfusion dependence (number of transfusions per year), splenectomy status, and hemoglobin levels pre- and post-splenectomy are key stratification criteria in mitapivat and gene therapy trials.

Hemolytic markers (LDH, indirect bilirubin, reticulocyte count, haptoglobin) measured at a stable baseline without recent illness or transfusion are used as primary endpoints and should be documented.