Pyruvate Kinase Deficiency of Red Cells

An autosomal recessive metabolic disorder caused by mutations in the PKLR gene (pyruvate kinase). It is the most common cause of hereditary nonspherocytic hemolytic anemia and is also the most frequent enzyme abnormality of GLYCOLYSIS. OMIM: 266200

Also Known As:

Networked: 360 relevant articles (18 outcomes, 40 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hemolytic Anemia
2.	Anemia
3.	Malaria
4.	Thalassemia
5.	Glucosephosphate Dehydrogenase Deficiency

Experts

1.	Bianchi, Paola: 16 articles (01/2020 - 06/2005)
2.	Fermo, Elisa: 13 articles (01/2020 - 06/2005)
3.	Barcellini, Wilma: 12 articles (01/2022 - 01/2013)
4.	Grace, Rachael F: 11 articles (01/2022 - 01/2018)
5.	Zanella, Alberto: 9 articles (01/2018 - 06/2005)
6.	Glader, Bertil: 8 articles (04/2021 - 01/2018)
7.	van Wijk, Richard: 8 articles (01/2020 - 02/2003)
8.	Chonat, Satheesh: 7 articles (01/2022 - 01/2018)
9.	van Beers, Eduard J: 7 articles (01/2022 - 01/2018)
10.	Al-Samkari, Hanny: 6 articles (01/2022 - 01/2021)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Pyruvate Kinase Deficiency of Red Cells:

1.	mitapivatIBA 01/01/2019 - "In this uncontrolled, phase 2 study, we evaluated the safety and efficacy of mitapivat in 52 adults with pyruvate kinase deficiency who were not receiving red-cell transfusions. " 01/01/2019 - "Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency." 11/09/2023 - "This study aimed to validate two new PRO instruments in adult patients enrolled in the ACTIVATE clinical trial (NCT03548220), where patients with PK deficiency received the drug mitapivat or a placebo. " 11/09/2023 - "This study aimed to psychometrically validate the first disease-specific patient-reported outcome (PRO) instruments: the 7-item PK Deficiency Diary (PKDD) and 12-item PK Deficiency Impact Assessment (PKDIA), designed to assess signs, symptoms, and impacts of PK deficiency in patients enrolled in the ACTIVATE global phase 3 study of mitapivat versus placebo (NCT03548220). " 11/01/2023 - "Based on findings from two phase III clinical trials, twice-daily oral mitapivat provided clinical benefit in adults with PK deficiency, both in patients not requiring, and requiring, regular RBC transfusions. "
2.	Pyruvate KinaseIBA 03/01/2022 - "The gold standard for the diagnosis of pyruvate kinase (PK) deficiency, the most frequent red blood cell enzymopathy, is an enzymatic activity assay. " 03/01/2010 - "Likewise, pyruvate kinase (PK) deficiency in humans is protective against Plasmodium replication in vitro. " 04/01/2008 - "The objective of this study was to examine clinical signs, laboratory parameters, and course of disease in Abyssinian and Somali cats with pyruvate kinase (PK) deficiency. " 09/01/2007 - "Considering the three previously described Irish cases of pyruvate kinase deficiency, this study raises the total number of pyruvate kinase-deficient Irish patients to seven in which a total of nine mutant PKLR alleles were identified. " 09/01/2003 - "In this study, possible adverse effects of pyruvate kinase (PK) deficiency on the maturation of erythroid progenitors were investigated. "
3.	Hemoglobins (Hemoglobin)IBA 01/01/2022 - "Secondary efficacy end points were the average change from baseline in the hemoglobin level, markers of hemolysis and hematopoiesis, and the change from baseline at week 24 in two pyruvate kinase deficiency-specific patient-reported outcome measures. " 08/01/1998 - "A case of severe pyruvate kinase deficiency anemia was managed conservatively without blood transfusions even though the hemoglobin concentration reached a nadir of 6.8 g/dL. " 11/01/2018 - "A total of 17047 cases were evaluated from 2009 to 2018 for thalassemia, hemoglobin variants, glucose 6 phosphate dehydrogenase deficiency, pyruvate kinase deficiency and hereditary spherocytosis. " 01/01/2018 - "Diagnostic testing for PK deficiency should be considered in patients with apparent congenital hemolytic anemia and close monitoring for iron overload, gallstones, and other complications is needed regardless of baseline hemoglobin. " 01/01/2019 - "The administration of mitapivat was associated with a rapid increase in the hemoglobin level in 50% of adults with pyruvate kinase deficiency, with a sustained response during a median follow-up of 29 months during the extension phase. "
4.	Adenosine Triphosphate (ATP)IBA 10/15/2009 - "Adenosine triphosphate depletion of erythrocytes simulates the phenotype associated with pyruvate kinase deficiency and confers protection against Plasmodium falciparum in vitro." 03/01/2015 - "Partial PK deficiency was associated with decreased red cell ATP content and markedly increased osmotic fragility. " 03/01/2013 - "In pyruvate kinase deficiency impaired production of adenosine triphosphate leads to destruction of red blood cells in the spleen or in the liver. " 11/01/2006 - "These cases also had a 3-4-fold increase in 2,3 DPG:ATP ratios, which is one of the additional indicators for PK deficiency. " 11/01/1986 - "In contrast, due to their decreased ATP and increased DPG concentrations, PK-deficient RBCs contain less aggregated PRPPS than do RBCs of comparable age without PK deficiency. "
5.	EnzymesIBA 02/23/1978 - "Human erythrocyte pyruvate kinase deficiency: the use of a kinetic study of mutant enzymes for the detection of heterozygotes." 02/15/1977 - "A Spanish family with erythrocyte pyruvate kinase deficiency: contribution of various immunologic methods in the study of the mutant enzyme." 04/01/1972 - "[Congenital pyruvate kinase deficiency in erythrocytes: kinetic study of the enzyme and metabolic consequences]." 01/01/2021 - "Historically, the investigation into pyruvate kinase deficiency (PKD) has been led by a red cell enzyme assay determining PK enzyme activity per unit of haemoglobin. " 10/01/2018 - "Red blood cell enzyme assay showed the presence of a significant increase in other enzyme activities, except for PK, suggesting a PK deficiency in the patient. "
6.	IsoenzymesIBA 12/01/2009 - "Rescue of pyruvate kinase deficiency in mice by gene therapy using the human isoenzyme." 09/01/1976 - "When combined in proband erythrocytes to the exclusion of any normal PK, the isoenzymes were associated with a severe chronic haemolytic process with many of the features of PK deficiency of the more common quantitative type. " 11/01/1975 - "In pyruvate kinase deficiency the high activity of the leucocyte isoenzyme may mask the erythrocyte defect. " 10/01/1975 - "Defective PK in the homozygous red cell was due to the absence of the erythrocyte PK isozyme and the compensatory presence of M2-type PK isozyme, as seen in the severe classical type PK deficiency in man." 02/01/1974 - "Erythrocyte pyruvate kinase deficiency associated with kinetically aberrant isozyme."
7.	Adenosine Diphosphate (ADP)IBA 01/01/1995 - "The dependence of the erythrocyte pyruvate kinase (PK)-catalyzed reaction on the glycolytic intermediates glucose-6-phosphate (Gluc-6-P), 2,3-diphosphoglycerate (2,3-DPG) and the nucleotides ADP and ATP was studied in normal individuals and 14 patients with PK deficiency. " 08/01/1981 - "Other nucleoside diphosphates normally capable of replacing ADP in the PK reaction were less effective with the mutant isozyme than with PK from controls or from subjects with other forms of PK deficiency, and Michaelis--Menten constants for several of these (UDP, GDP, CDP) were significantly elevated. " 08/01/1989 - "The following hematological and enzyme kinetic parameters can serve to identify heterozygotes for PK deficiency: 1) a slight reticulocytosis, 2) an up-to-twofold increase of the intracellular concentrations of glucose-6-phosphate in the erythrocyte, 3) a mixed cooperativity of the phosphoenolpyruvate (PEP)-binding process of PK, 4) a decreased nucleotide specificity with guanosine diphosphate and uridine diphosphate, and 5) a lowered affinity for adenosine diphosphate. "
8.	Uridine Diphosphate (UDP)IBA 08/01/1981 - "Other nucleoside diphosphates normally capable of replacing ADP in the PK reaction were less effective with the mutant isozyme than with PK from controls or from subjects with other forms of PK deficiency, and Michaelis--Menten constants for several of these (UDP, GDP, CDP) were significantly elevated. " 08/01/1989 - "The following hematological and enzyme kinetic parameters can serve to identify heterozygotes for PK deficiency: 1) a slight reticulocytosis, 2) an up-to-twofold increase of the intracellular concentrations of glucose-6-phosphate in the erythrocyte, 3) a mixed cooperativity of the phosphoenolpyruvate (PEP)-binding process of PK, 4) a decreased nucleotide specificity with guanosine diphosphate and uridine diphosphate, and 5) a lowered affinity for adenosine diphosphate. "
9.	Complement Receptors (Complement Receptor)IBA 08/01/2006 - "The past few years have seen significant progress towards achieving this goal for some of the best-known malaria resistance genes that determine the structure or function of red blood cells: Gerbich blood group antigen negativity; polymorphisms of the complement receptor genes (most notably CR1); Southeast Asian ovalocytosis; pyruvate kinase deficiency; haemoglobin E; the sickle cell trait; and alpha-thalassaemia are all examples. " 11/01/2010 - "Some of the mechanisms underlying protection against this disease are described in this review for hemoglobin-inherited disorders (thalassemia, sickle-cell trait, HbC and HbE), erythrocyte polymorphisms (ovalocytosis and Duffy blood group), enzymopathies (G6PD deficiency and PK deficiency) and immunogenetic variants (HLA alleles, complement receptor 1, NOS2, tumor necrosis factor-α promoter and chromosome 5q31-q33 polymorphisms)."
10.	Guanosine Diphosphate (GDP)IBA 08/01/1981 - "Other nucleoside diphosphates normally capable of replacing ADP in the PK reaction were less effective with the mutant isozyme than with PK from controls or from subjects with other forms of PK deficiency, and Michaelis--Menten constants for several of these (UDP, GDP, CDP) were significantly elevated. " 08/01/1989 - "The following hematological and enzyme kinetic parameters can serve to identify heterozygotes for PK deficiency: 1) a slight reticulocytosis, 2) an up-to-twofold increase of the intracellular concentrations of glucose-6-phosphate in the erythrocyte, 3) a mixed cooperativity of the phosphoenolpyruvate (PEP)-binding process of PK, 4) a decreased nucleotide specificity with guanosine diphosphate and uridine diphosphate, and 5) a lowered affinity for adenosine diphosphate. "

Therapies and Procedures

1.	Therapeutics 10/18/2021 - "Even rare anaemias such as pyruvate kinase deficiency have promising clinical trials with targeted therapies. " 01/01/2023 - "The long-term effect of treatment with disease-modifying therapy in PK deficiency will require continued evaluation." 01/01/2022 - "Pyruvate kinase deficiency: clinical expression and new therapies." 01/01/2022 - "The treatment of PK deficiency has made strides over the last few years with newer disease-modifying therapies being developed and studied, with the potential to change the course of disease in childhood and beyond." 01/01/2017 - "There are currently no targeted therapies for PK deficiency. "
2.	Splenectomy 07/01/2021 - "Single port robotic splenectomy for pyruvate kinase deficiency in a five-year-old patient, a case report of a surgical first." 10/01/2018 - "After a clear diagnosis of PK deficiency, the patient underwent splenectomy." 01/01/2017 - "The concomitant defects did not aggravate the clinical phenotype; however, in one patient, the initial diagnosis of pyruvate kinase deficiency delayed the correct diagnosis of HX for many years and resulted in splenectomy followed by thrombotic complications. " 07/01/2001 - "Recurrent thromboembolic disease following splenectomy for pyruvate kinase deficiency." 05/01/1978 - "Erythrocyte populations in pyruvate kinase deficiency anaemia following splenectomy. "
3.	Blood Transfusion (Blood Transfusions) 01/01/2022 - "With a presumptive diagnosis of pyruvate kinase deficiency (PK), the patient had been splenectomised at 7 years of age with a partial recovery of the anaemia and a decrease of the blood transfusion rate. " 04/01/1997 - "The authors report a case of pyruvate kinase deficiency in a 4-year-old patient who required monthly blood transfusions. " 01/01/1997 - "The diagnosis of red cell pyruvate kinase deficiency and the exclusion of Hb H disease was achieved after cessation of blood transfusion for 3 months. " 09/01/2003 - "A 4-year-old Japanese girl with severe PK deficiency underwent splenectomy to reduce her need for blood transfusions. " 08/01/1998 - "In cases of severe pyruvate kinase deficiency anemia, pregnancy per se might not be an indication for prophylactic blood transfusions."
4.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 09/01/2000 - "Successful bone marrow transplantation in a child with red blood cell pyruvate kinase deficiency." 12/01/1995 - "The anemia and PK deficiency of CBA-Pk-1slc/Pk-1slc mice were cured by bone marrow transplantation (BMT) from CBA-(+/+) mice. " 05/06/2020 - "Successful allogeneic bone marrow transplantation using immunosuppressive conditioning regimen for a patient with red blood cell transfusiondependent pyruvate kinase deficiency anemia."
5.	Ketogenic Diet 12/01/2020 - "The author regret that, in the section "Dietary treatments" the sentence "Ketogenic diet is the gold standard therapy for Glut 1 deficiency and pyruvate kinase deficiency but it can be also applied in severe drug-resistant epileptic encephalopathies [4]." is not correct."