Pyruvate Kinase Deficiency: Current Challenges and Future Prospects

References

• Grace RF, Bianchi P, van Beers EJ., et al. Clinical spectrum of pyruvate kinase deficiency: data from the pyruvate kinase deficiency natural history study. Blood. 2018;131(20):2183–2192.
   PubMed Web of Science ®Google Scholar
• Grace RF, Barcellini W. Management of pyruvate kinase deficiency in children and adults. Blood. 2020;136(11):1241–1249.
   PubMed Web of Science ®Google Scholar
• Grace RF, Mark Layton D, Barcellini W. How we manage patients with pyruvate kinase deficiency. Br J Haematol. 2019;184(5):721–734.
   PubMed Web of Science ®Google Scholar
• Fattizzo B, Giannotta JA, Cecchi N, Barcellini W. Confounding factors in the diagnosis and clinical course of rare congenital hemolytic anemias. Orphanet J Rare Dis. 2021;16(1):415.
   PubMed Web of Science ®Google Scholar
• Grace RF, Rose C, Layton DM, et al. Safety and efficacy of mitapivat in pyruvate kinase deficiency. N Engl J Med. 2019;381(10):933–944.
   PubMed Web of Science ®Google Scholar
• Schwartz JD, Barcellini W, Grace RF, et al. Who should be eligible for gene therapy clinical trials in red blood cell pyruvate kinase deficiency (PKD)?: toward an expanded definition of severe PKD. Am J Hematol. 2022;97(3):E120–E125.
   PubMed Web of Science ®Google Scholar
• Beutler E, Gelbart T. Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population. Blood. 2000;95(11):3585–3588.
   PubMed Web of Science ®Google Scholar
• Carey PJ, Chandler J, Hendrick A, et al. Northern Region Haematologists Group. Prevalence of pyruvate kinase deficiency in Northern European population in the north of England. Blood. 2000;96(12):4005–4006.
   PubMed Web of Science ®Google Scholar
• Ayi K, Min-Oo G, Serghides L, et al. Pyruvate kinase deficiency and malaria. N Engl J Med. 2008;358(17):1805–1810.
   PubMed Web of Science ®Google Scholar
• Min-Oo G, Fortin A, Tam MF, Nantel A, Stevenson MM, Gros P. Pyruvate kinase deficiency in mice protects against malaria. Nat Genet. 2003;35(4):357–362.
   PubMed Web of Science ®Google Scholar
• Qidwai T, Jamal F, Singh S. Exploring putative molecular mechanisms of human pyruvate kinase enzyme deficiency and its role in resistance against Plasmodium falciparum malaria. Interdiscip Sci. 2014;6(2):158–166.
   PubMed Web of Science ®Google Scholar
• Machado P, Manco L, Gomes C, et al. Pyruvate kinase deficiency in sub-Saharan Africa: identification of a highly frequent missense mutation (G829A;Glu277Lys) and association with malaria. PLoS One. 2012;7(10):e47071.
   PubMed Web of Science ®Google Scholar
• van Bruggen R, Gualtieri C, Iliescu A, et al. Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR) Variants in a Thai Population. PLoS One. 2015;10(12):e0144555.
   PubMed Web of Science ®Google Scholar
• Zanella A, Fermo E, Bianchi P, Chiarelli LR, Valentini G. Pyruvate kinase deficiency: the genotype-phenotype association. Blood Rev. 2007;21(4):217–231.
   PubMed Web of Science ®Google Scholar
• Zanella A, Bianchi P, Fermo E. Pyruvate kinase deficiency. Haematologica. 2007;92(6):721–723.
   PubMed Web of Science ®Google Scholar
• Grace RF, Zanella A, Neufeld EJ, et al. Erythrocyte pyruvate kinase deficiency: 2015 status report. Am J Hematol. 2015;90(9):825–830.
   PubMed Web of Science ®Google Scholar
• Bianchi P, Fermo E, Lezon-Geyda K, et al. Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency. Am J Hematol. 2020;95(5):472–482.
   PubMed Web of Science ®Google Scholar
• Al-Samkari H, van Beers EJ, Morton DH, et al. Characterization of the severe phenotype of pyruvate kinase deficiency. Am J Hematol. 2020. doi:10.1002/ajh.25926
   Web of Science ®Google Scholar
• Zanella A, Fermo E, Bianchi P, Valentini G. Red cell pyruvate kinase deficiency: molecular and clinical aspects. Br J Haematol. 2005;130(1):11–25.
   PubMed Web of Science ®Google Scholar
• Grace RF, Cohen J, Egan S, et al. The burden of disease in pyruvate kinase deficiency: patients’ perception of the impact on health-related quality of life. Eur J Haematol. 2018;101(6):758–765.
   PubMed Web of Science ®Google Scholar
• Barcellini W, Fattizzo B. Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia. Dis Markers. 2015;2015:635670.
   PubMed Web of Science ®Google Scholar
• van Beers EJ, van Straaten S, Morton DH, et al. Prevalence and management of iron overload in pyruvate kinase deficiency: report from the Pyruvate Kinase Deficiency Natural History Study. Haematologica. 2019;104(2):e51–e53.
   PubMed Web of Science ®Google Scholar
• Beutler E. Red Cell Metabolism. A Manual of Biochemical Methods. 3rd ed. New York: Grune and Stratton, Inc; 1984:188.
   Google Scholar
• Bianchi P, Zanella A. Hematologically important mutations: red cell pyruvate kinase (third update). Blood Cells Mol Dis. 2000;26(1):47–53.
   PubMed Web of Science ®Google Scholar
• Perkins A, Xu X, Higgs DR, et al. KLF1 Consensus Workgroup. Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants. Blood. 2016;127(15):1856–1862.
   PubMed Web of Science ®Google Scholar
• Rider NL, Strauss KA, Brown K, et al. Erythrocyte pyruvate kinase deficiency in an old-order Amish cohort: longitudinal risk and disease management. Am J Hematol. 2011;86(10):827–834.
   PubMed Web of Science ®Google Scholar
• Iolascon A, Andolfo I, Barcellini W, et al. Working Study Group on Red Cells and Iron of the EHA. Recommendations regarding splenectomy in hereditary hemolytic anemias. Haematologica. 2017;102(8):1304–1313.
   PubMed Web of Science ®Google Scholar
• Sandoval C, Stringel G, Weisberger J, Jayabose S. Failure of partial splenectomy to ameliorate the anemia of pyruvate kinase deficiency. J Pediatr Surg. 1997;32:641–642.
   PubMed Web of Science ®Google Scholar
• Zahid MF, Bains APS. Rapidly fatal Klebsiella pneumoniae sepsis in a patient with pyruvate kinase deficiency and asplenia. Blood. 2017;130(26):2906.
   PubMed Web of Science ®Google Scholar
• Kristinsson SY, Gridley G, Hoover RN, Check D, Landgren O. Long-term risks after splenectomy among 8149 cancer-free American veterans: a cohort study with up to 27 years follow-up. Haematologica. 2014;99(2):392–398.
   PubMed Web of Science ®Google Scholar
• Lin JN, Chen HJ, Lin MC, et al. Risk of venous thromboembolism in patients with splenic injury and splenectomy. A nationwide cohort study. Thromb Haemost. 2016;115(1):176–183.
   PubMed Web of Science ®Google Scholar
• Chou R, DeLoughery TG. Recurrent thromboembolic disease following splenectomy for pyruvate kinase deficiency. Am J Hematol. 2001;67(3):197–199.
   PubMed Web of Science ®Google Scholar
• Morimoto M, Kanno H, Asai H, et al. Pyruvate kinase deficiency of mice associated with nonspherocytic hemolytic anemia and cure of the anemia by marrow transplantation without host irradiation. Blood. 1995;86(11):4323–4330.
   PubMed Web of Science ®Google Scholar
• Tanphaichitr VS, Suvatte V, Issaragrisil S, et al. Successful bone marrow transplantation in a child with red blood cell pyruvate kinase deficiency. Bone Marrow Transplant. 2000;26(6):689–690.
   PubMed Web of Science ®Google Scholar
• van Straaten S, Bierings M, Bianchi P, et al. Worldwide study of hematopoietic allogeneic stem cell transplantation in pyruvate kinase deficiency. Haematologica. 2018;103(2):e82–e86.
   PubMed Web of Science ®Google Scholar
• Del Giudice EM, Perrotta S, Nobili B, Specchia C. d’Urzo G, Iolascon, A. Coinheritance of Gilbert syndrome increases the risk for developing gallstones in patients with hereditary spherocytosis. Blood. 1999;94:2259–2262.
   PubMed Web of Science ®Google Scholar
• Haverfield EV, McKenzie CA, Forrester T, et al. UGT1A1 variation and gallstone formation in sickle cell disease. Blood. 2005;105:968–972.
   PubMed Web of Science ®Google Scholar
• Plensa E, Tapia G, Juncà J, Pèrez R, Castellà E, Martì S. Paravertebral extramedullary hematopoiesis due to pyruvate kinase deficiency. Haematologica. 2005;90(suppl):ECR32.
   PubMedGoogle Scholar
• Rutgers MJ, van der Lugt PJ, van Turnhout JM. Spinal cord compression by extramedullary hemopoietic tissue in pyruvate-kinase-deficiency-caused hemolytic anemia. Neurology. 1979;29(4):510–513.
   PubMed Web of Science ®Google Scholar
• Bachmeyer C, Khalil A, Kerrou K, Girot R, Gounant V. Idiopathic pulmonary arterial hypertension in a patient with pyruvate kinase deficiency and paravertebral extramedullary hematopoiesis. Annals Hematol. 2009;88:603–605.
   PubMed Web of Science ®Google Scholar
• Müller-Soyano A. Tovar de Roura E, Duke PR, et al. Pyruvate kinase deficiency and leg ulcers. Blood. 1976;47(5):807–813.
   PubMed Web of Science ®Google Scholar
• Kung C, Hixon J, Kosinski PA, et al. AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency. Blood. 2017;130(11):1347–1356.
   PubMed Web of Science ®Google Scholar
• Al-Samkari H, Galactéros F, Glenthøj A, et al. Mitapivat versus Placebo for Pyruvate Kinase Deficiency. N Engl J Med. 2022;386(15):1432–1442.
   PubMed Web of Science ®Google Scholar
• Glenthøj A, van Beers EJ, Al-Samkari H, et al. ACTIVATE-T: a phase 3, open-label, multicenter study of mitapivat in adults with pyruvate kinase deficiency who are regularly transfused. Eur Hematol Assoc. 2021;9:17.
   Google Scholar
• Grace RF, Glenthoej A, Barcellini W, et al. Durability of Hemoglobin Response and Reduction in Transfusion Burden Is Maintained over Time in Patients with Pyruvate Kinase Deficiency Treated with Mitapivat in a Long-Term Extension Study. Am Soc Hematol. 2021;138:848.
   Google Scholar
• Xu JZ, Conrey A, Frey I, et al. Mitapivat (AG-348) demonstrates safety, tolerability, and improvements in anemia, hemolysis, oxygen affinity, and hemoglobin S polymerization kinetics in adults with sickle cell disease: a Phase 1 dose escalation study. Am Soc Hematol. 2021;138:10.
   Google Scholar
• Kuo KH, Layton DM, Lal A, et al. Results from a phase 2, open-label, multicenter study of the oral pyruvate kinase inhibitor mitapivat in adults with non-transfusion-dependent alpha- or beta-thalassemia. Eur Hematol Assoc. 2021;5:92.
   Google Scholar
• Brown RCC, Saraf SL, Cruz K, et al. Activation of Pyruvate Kinase-R with Etavopivat (FT-4202) Is Well Tolerated, Improves Anemia, and Decreases Intravascular Hemolysis in Patients with Sickle Cell Disease Treated for up to 12 Weeks. Am Soc Hematol. 2021;138:9.
   Google Scholar
• Garcia-Gomez M, Calabria A, Garcia-Bravo M, et al. Safe and efficient gene therapy for pyruvate kinase deficiency. Mol Ther. 2016;24(7):1187–1198.
   PubMed Web of Science ®Google Scholar
• Shah AJ, López Lorenzo JL, Navarro S, et al. Lentiviral mediated gene therapy for pyruvate kinase deficiency: interim results of a global phase 1 study for adult and pediatric patients. Am Soc Hematol. 2021;138:563.
   Google Scholar
• Al-Samkari H, van Beers EJ, Morton DH, et al. Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency. Blood Adv. 2022;6(6):1844–1853.
   PubMed Web of Science ®Google Scholar
• Salek MS, Ionova T, Johns JR, Oliva EN. Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in Phase II and III clinical trials of pyruvate kinase deficiency. Qual Life Res. 2019;28(2):399–410.
   PubMed Web of Science ®Google Scholar
• Salek S, Boscoe AN, Piantedosi S, et al. Development of the pyruvate kinase deficiency diary and pyruvate kinase deficiency impact assessment: disease-specific assessments. Eur J Haematol. 2020;104(5):427–434.
   PubMed Web of Science ®Google Scholar
• Motta I, Giannotta J, Ferraresi M, et al. Autoimmune hemolytic anemia as a complication of congenital anemias. a case series and review of the literature. J Clin Med. 2021;10(15):3439.
   PubMed Web of Science ®Google Scholar