Management of pyruvate kinase deficiency in children and adults

Blood. 2020 Sep 10;136(11):1241-1249. doi: 10.1182/blood.2019000945.


Pyruvate kinase deficiency (PKD) is an autosomal-recessive enzyme defect of the glycolytic pathway that causes congenital nonspherocytic hemolytic anemia. The diagnosis and management of patients with PKD can be challenging due to difficulties in the diagnostic evaluation and the heterogeneity of clinical manifestations, ranging from fetal hydrops and symptomatic anemia requiring lifelong transfusions to fully compensated hemolysis. Current treatment approaches are supportive and include transfusions, splenectomy, and chelation. Complications, including iron overload, bilirubin gallstones, extramedullary hematopoiesis, pulmonary hypertension, and thrombosis, are related to the chronic hemolytic anemia and its current management and can occur at any age. Disease-modifying therapies in clinical development may decrease symptoms and findings associated with chronic hemolysis and avoid the complications associated with current treatment approaches. As these disease-directed therapies are approved for clinical use, clinicians will need to define the types of symptoms and findings that determine the optimal patients and timing for initiating these therapies. In this article, we highlight disease manifestations, monitoring approaches, strategies for managing complications, and novel therapies in development.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Hemolytic, Congenital Nonspherocytic / diagnosis
  • Anemia, Hemolytic, Congenital Nonspherocytic / epidemiology
  • Anemia, Hemolytic, Congenital Nonspherocytic / surgery
  • Anemia, Hemolytic, Congenital Nonspherocytic / therapy*
  • Blood Transfusion
  • Chelation Therapy
  • Child
  • Child, Preschool
  • Cholelithiasis / etiology
  • Cholelithiasis / surgery
  • Clinical Trials as Topic
  • Disease Management
  • Female
  • Fetal Diseases / genetics
  • Genetic Therapy
  • Genotype
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Infant, Newborn
  • Iron Chelating Agents / therapeutic use
  • Iron Overload / drug therapy
  • Iron Overload / etiology
  • Jaundice, Neonatal / etiology
  • Jaundice, Neonatal / therapy
  • Male
  • Mutation
  • Pregnancy
  • Prevalence
  • Pyruvate Kinase / deficiency*
  • Pyruvate Kinase / genetics
  • Pyruvate Metabolism, Inborn Errors / diagnosis
  • Pyruvate Metabolism, Inborn Errors / epidemiology
  • Pyruvate Metabolism, Inborn Errors / surgery
  • Pyruvate Metabolism, Inborn Errors / therapy*
  • Splenectomy
  • Splenomegaly / etiology
  • Splenomegaly / surgery


  • Iron Chelating Agents
  • PKLR protein, human
  • Pyruvate Kinase

Supplementary concepts

  • Pyruvate Kinase Deficiency of Red Cells