551 results match your criteria Pyruvate Kinase Deficiency


Mitapivat versus Placebo for Pyruvate Kinase Deficiency. Reply.

N Engl J Med 2022 Jun;386(26):2539

University Medical Center Utrecht, Utrecht, the Netherlands.

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Mitapivat versus Placebo for Pyruvate Kinase Deficiency.

N Engl J Med 2022 Jun;386(26):2538-2539

Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain.

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Iron overload disorders.

Hepatol Commun 2022 Jun 14. Epub 2022 Jun 14.

Liver Institute Northwest and Elson S. Floyd College of Medicine, Washington State University, Washington, USA.

Iron overload disorders represent a variety of conditions that lead to increased total body iron stores and resultant end-organ damage. An elevated ferritin and transferrin-iron saturation can be commonly encountered in the evaluation of elevated liver enzymes. Confirmatory homeostatic iron regulator (HFE) genetic testing for C282Y and H63D, mutations most encountered in hereditary hemochromatosis, should be pursued in evaluation of hyperferritinemia. Read More

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Efficient and Fast Generation of Relevant Disease Mouse Models by and Gene Editing of Zygotes.

CRISPR J 2022 06;5(3):422-434

Cell Technology Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIEMAT/CIBERER), Madrid, Spain.

Knockout mice for human disease-causing genes provide valuable models in which new therapeutic approaches can be tested. Electroporation of genome editing tools into zygotes, or within oviducts, allows for the generation of targeted mutations in a shorter time. We have generated mouse models deficient in genes involved in metabolic rare diseases (Primary Hyperoxaluria Type 1 Pyruvate Kinase Deficiency) or in a tumor suppressor gene (). Read More

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Novel Compound Heterozygous Mutation Induced Pyruvate Kinase Deficiency With Persistent Pulmonary Hypertension in a Neonate: A Case Report.

Front Cardiovasc Med 2022 26;9:872172. Epub 2022 Apr 26.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: Pulmonary hypertension could be associated with pyruvate kinase deficiency (PKD). There are few reported cases of PPHN as the first clinical manifestation of PKD. Herein we report a rare case of PKD in which the patient exhibited persistent pulmonary hypertension in the neonate (PPHN), and genetic testing helped to rapidly identify an potential association. Read More

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Fetal Pyruvate Kinase Deficiency Identified Incidentally in a Chinese Family at Risk for α-Thalassemia.

Indian J Hematol Blood Transfus 2022 Apr 30;38(2):424-426. Epub 2021 Nov 30.

Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Jinsui Road 9, Guangzhou, 510623 Guangdong China.

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Diagnosis, monitoring, and management of pyruvate kinase deficiency in children.

Pediatr Blood Cancer 2022 Aug 22;69(8):e29696. Epub 2022 Apr 22.

Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, Texas, USA.

Pyruvate kinase (PK) deficiency is a rare, congenital red blood cell disorder caused by a single gene defect. The spectrum of genotypes, variants, and phenotypes are broad, commonly requiring a multimodal approach including enzyme and genetic testing for accurate and reliable diagnosis. Similarly, management of primary and secondary sequelae of PK deficiency varies, mainly including supportive care with transfusions and surgical interventions to improve symptoms and quality of life. Read More

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Gene Editing for Inherited Red Blood Cell Diseases.

Front Physiol 2022 28;13:848261. Epub 2022 Mar 28.

Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.

Today gene therapy is a real therapeutic option to address inherited hematological diseases that could be beneficial for thousands of patients worldwide. Currently, gene therapy is used to treat different monogenic hematological pathologies, including several red blood cell diseases such as β-thalassemia, sickle cell disease and pyruvate kinase deficiency. This approach is based on addition gene therapy, which consists of the correction of hematopoietic stem cells (HSCs) using lentiviral vectors, which integrate a corrected version of the altered gene. Read More

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Mitapivat versus Placebo for Pyruvate Kinase Deficiency.

N Engl J Med 2022 04;386(15):1432-1442

From the Division of Hematology Oncology, Massachusetts General Hospital (H.A.-S.) and the Dana-Farber/Boston Children's Cancer and Blood Disorders Center (R.F.G.), Harvard Medical School, Boston, and Agios Pharmaceuticals, Cambridge (M.P.J., E.Z., R.X., P.H., V.B., S.G.) - all in Massachusetts; Unité des Maladies Génétiques du Globule Rouge, Centre Hospitalier Universitaire Henri Mondor, Créteil, France (F.G.); the Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen (A.G.); Duke University Medical Center, Durham, NC (J.A.R.); the Department of Pediatrics, University of Würzburg, Würzburg, Germany (O.A.); the Hematology Department, Hospital Universitario La Paz, Madrid (M.M.-A.); Hammersmith Hospital, Imperial College Healthcare NHS Trust, London (D.M.L.); Tohoku University Hospital, Sendai, Japan (K.O.); McMaster University, Hamilton, ONT, Canada (M.V.); Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan (W.B.); Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, and the Department of Pediatrics, Emory University, Atlanta (S.C.); and the Benign Hematology Center, Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, Utrecht, the Netherlands (E.J.B.).

Background: Pyruvate kinase deficiency is a rare, hereditary, chronic condition that is associated with hemolytic anemia. In a phase 2 study, mitapivat, an oral, first-in-class activator of erythrocyte pyruvate kinase, increased the hemoglobin level in patients with pyruvate kinase deficiency.

Methods: In this global, phase 3, randomized, placebo-controlled trial, we evaluated the efficacy and safety of mitapivat in adults with pyruvate kinase deficiency who were not receiving regular red-cell transfusions. Read More

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Concomitant Hereditary Spherocytosis and Pyruvate Kinase Deficiency in a Spanish Family with Chronic Hemolytic Anemia: Contribution of Laser Ektacytometry to Clinical Diagnosis.

Cells 2022 03 28;11(7). Epub 2022 Mar 28.

Pediatric Hematology Department, University Hospital Mútua Terrassa Terrassa, 08221 Barcelona, Spain.

Background: Hereditary spherocytosis (HS) and pyruvate kinase deficiency (PKD) are the most common causes of hereditary chronic hemolytic anemia. Here, we describe clinical and genetic characteristics of a Spanish family with concomitant β-spectrin (SPTB) c.647G>A variant and pyruvate kinase (PKLR) c. Read More

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Synthetic Red Blood Cell-Specific Glycolytic Intermediate 2,3-Diphosphoglycerate (2,3-DPG) Inhibits Development .

Front Cell Infect Microbiol 2022 15;12:840968. Epub 2022 Mar 15.

Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisbon, Portugal.

Mechanisms of malaria parasite interaction with its host red blood cell may provide potential targets for new antimalarial approaches. Pyruvate kinase deficiency has been associated with resistance to malaria in both experimental models and population studies. Two of the major pyruvate kinase deficient-cell disorders are the decrease in ATP and the increase in 2,3-biphosphoglycerate (2,3-BPG) concentration. Read More

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Next generation sequencing for diagnosis of hereditary anemia: Experience in a Spanish reference center.

Clin Chim Acta 2022 Jun 26;531:112-119. Epub 2022 Mar 26.

Sociedad de Hematología y Hemoterapia, Madrid, Spain.

Background And Aims: Hereditary anemia (HA) encloses a wide group of rare inherited disorders with clinical and hematologic overlaps that complicate diagnosis.

Materials And Methods: A 48-gene panel was developed to diagnose HA by Next Generation Sequencing (NGS) in a large cohort of 165 patients from 160 unrelated families.

Results: Patients were divided in: A) patients who had a suspicion of a specific type of HA (n = 109), and B) patients who had a suspicion of HA but with no clear type (n = 56). Read More

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A novel homozygous missense variant p.D339N in the PKLR gene correlates with pyruvate kinase deficiency in a Pakistani family: a case report.

J Med Case Rep 2022 Feb 16;16(1):66. Epub 2022 Feb 16.

Department of Biotechnology, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan.

Background: Pyruvate kinase deficiency is an exceptionally rare autosomal recessive Mendelian disorder caused by bi-allelic pathogenic variants in the PKLR gene. It is mainly characterized by chronic nonspherocytic hemolytic anemia though other symptoms such as splenomegaly, hepatomegaly, pallor, fatigue, iron overload, shortness of breath, hyperbilirubinemia, and gallstones might also prevail.

Case Presentation: We present here a novel genetic defect in the PKLR gene that correlates with pyruvate kinase deficiency phenotype in a consanguineous family from North-Western Pakistan. Read More

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February 2022

Novel missense mutation (A300P) causing pyruvate kinase deficiency in an Omani Kindred-PK deficiency masquerading as congenital dyserythropoietic anemia.

Clin Case Rep 2022 Feb 7;10(2):e05315. Epub 2022 Feb 7.

Dipartimento di Medicina Molecolare e Biotecnologie Mediche Università di Napoli Federico II Napoli Italy.

We report herein a child with transfusion-dependent chronic anemia, the cause of which was difficult to establish because of his transfusion dependency. The clinical and laboratory features suggested a chronic nonspherocytic hemolytic anemia (CNSHA) with bone marrow features suggestive of congenital dyserythropoietic anemia (CDA). DNA studies, however, revealed the underlying condition to be due to a novel mutation in the gene responsible for pyruvate kinase deficiency (PKD). Read More

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February 2022

Haemoglobin Bristol-Alesha in a child with non-spherocytic severe haemolytic anaemia and marked anisochromic poikilocytosis with basophilic stippling and amorphous intracellular content.

Blood Cells Mol Dis 2022 05 22;94:102652. Epub 2022 Jan 22.

Centre for Haematology, St Mary's Hospital, Campus of Imperial College, London, United Kingdom of Great Britain and Northern Ireland.

Here we describe a retrospective study of a 10-year-old girl, adopted from India, and referred to the Rare Anemias Unit for the diagnosis of a severe haemolytic anaemia of unknown etiology. Blood film examination revealed markedly abnormal red cell morphology characterised by a mixture of very pale (hypochromic) cells with basophilic stippling and macrocytic cells containing coarse basophilic dots and an amorphous material of unknown origin. 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. Read More

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Mitapivat, a novel pyruvate kinase activator, for the treatment of hereditary hemolytic anemias.

Ther Adv Hematol 2021 21;12:20406207211066070. Epub 2021 Dec 21.

Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands.

Mitapivat (AG-348) is a novel, first-in-class oral small molecule allosteric activator of the pyruvate kinase enzyme. Mitapivat has been shown to significantly upregulate both wild-type and numerous mutant forms of erythrocyte pyruvate kinase (PKR), increasing adenosine triphosphate (ATP) production and reducing levels of 2,3-diphosphoglycerate. Given this mechanism, mitapivat has been evaluated in clinical trials in a wide range of hereditary hemolytic anemias, including pyruvate kinase deficiency (PKD), sickle cell disease, and the thalassemias. Read More

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December 2021

Generation and Export of Red Blood Cell ATP in Health and Disease.

Front Physiol 2021 5;12:754638. Epub 2021 Nov 5.

Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Durham VA and Duke University Medical Centers, Durham, NC, United States.

Metabolic homeostasis in animals depends critically on evolved mechanisms by which red blood cell (RBC) hemoglobin (Hb) senses oxygen (O) need and responds accordingly. The entwined regulation of ATP production and antioxidant systems within the RBC also exploits Hb-based O-sensitivity to respond to various physiologic and pathophysiologic stresses. O offloading, for example, promotes glycolysis in order to generate both 2,3-DPG (a negative allosteric effector of Hb O binding) and ATP. Read More

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November 2021

Red Blood Cell Metabolism in Pyruvate Kinase Deficient Patients.

Front Physiol 2021 21;12:735543. Epub 2021 Oct 21.

Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States.

Pyruvate kinase deficiency (PKD) is the most frequent congenital enzymatic defect of glycolysis, and one of the most common causes of hereditary non spherocytic hemolytic anemia. Therapeutic interventions are limited, in part because of the incomplete understanding of the molecular mechanisms that compensate for the metabolic defect. Mass spectrometry-based metabolomics analyses were performed on red blood cells (RBCs) from healthy controls (=10) and PKD patients (=5). Read More

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October 2021

[Hereditary anaemias].

Ugeskr Laeger 2021 10;183(42)

Hereditary anaemias are the most prevalent genetic disorders worldwide. Until recently, treatment options were mostly supportive or surgical, i.e. Read More

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October 2021

Severe Presentation of Congenital Hemolytic Anemias in the Neonatal Age: Diagnostic and Therapeutic Issues.

Diagnostics (Basel) 2021 Aug 26;11(9). Epub 2021 Aug 26.

Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.

Congenital hemolytic anemias (CHAs) are a group of diseases characterized by premature destruction of erythrocytes as a consequence of intrinsic red blood cells abnormalities. Suggestive features of CHAs are anemia and hemolysis, with high reticulocyte count, unconjugated hyperbilirubinemia, increased lactate dehydrogenase (LDH), and reduced haptoglobin. The peripheral blood smear can help the differential diagnosis. Read More

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Preclinical studies of efficacy thresholds and tolerability of a clinically ready lentiviral vector for pyruvate kinase deficiency treatment.

Mol Ther Methods Clin Dev 2021 Sep 29;22:350-359. Epub 2021 Jul 29.

Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, Spain.

Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disorder caused by mutations in the gene. PKD is characterized by non-spherocytic hemolytic anemia of variable severity and may be fatal in some cases during early childhood. Although not considered the standard of care, allogeneic stem cell transplantation has been shown as a potentially curative treatment, limited by donor availability, toxicity, and incomplete engraftment. Read More

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September 2021

Clinically relevant gene editing in hematopoietic stem cells for the treatment of pyruvate kinase deficiency.

Mol Ther Methods Clin Dev 2021 Sep 14;22:237-248. Epub 2021 May 14.

Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid 28040, Spain.

Pyruvate kinase deficiency (PKD), an autosomal-recessive disorder, is the main cause of chronic non-spherocytic hemolytic anemia. PKD is caused by mutations in the pyruvate kinase, liver and red blood cell ( ) gene, which encodes for the erythroid pyruvate kinase protein (RPK). RPK is implicated in the last step of anaerobic glycolysis in red blood cells (RBCs), responsible for the maintenance of normal erythrocyte ATP levels. Read More

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September 2021

Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency.

Blood Adv 2022 03;6(6):1844-1853

Dana-Farber Boston Children's Cancer and Blood Disorder Center, Harvard Medical School, Boston, MA.

Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic hemolytic anemia. Although recognition of the disease spectrum has recently expanded, data describing its impact on health-related quality of life (HRQoL) are limited. In this prospective international cohort of 254 patients (131 adults and 123 children) with PKD, we used validated measures to assess the impact of disease on HRQoL (EuroQol 5-Dimension Questionnaire, Pediatric Quality of Life Inventory Generic Core Scale version 4. Read More

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Lemierre Syndrome in a Patient With Splenectomy Secondary to Pyruvate Kinase Deficiency, Complicated by Heparin Resistance.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211040635

Kern Medical, Bakersfield, CA, USA.

Lemierre syndrome was first documented in the literature in 1936, and is defined as septic thrombophlebitis of the internal jugular vein. It is typically a result of oropharyngeal infection causing local soft tissue inflammation, which spreads to vasculature, and promotes formation of septic thrombi within the lumen, persistent bacteremia, and septic emboli. We present the case of a 24-year-old incarcerated man, who presented with leukocytosis and a right-sided tender, swollen neck after undergoing left mandibular molar extraction for an infected tooth. Read More

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October 2021

A Sri Lankan girl with a new genetic variant in the PKLR gene causing pyruvate kinase deficiency: a case report.

J Med Case Rep 2021 Jul 27;15(1):374. Epub 2021 Jul 27.

Department of Molecular Pathology, Viapath at King's College Hospital, King's College Hospital, London, SE5 9RS, UK.

Background: Erythrocyte pyruvate kinase is expressed under the control of the PKLR gene located on chromosome 1q21. Pyruvate kinase catalyzes the final steps of the glycolytic pathway and creates 50% of the red cell total adenosine triphosphate. Pyruvate kinase deficiency is the commonest glycolytic defect causing congenital non-spherocytic hemolytic anemia inherited in an autosomal recessive trait in which homozygotes and compound heterozygotes are common. Read More

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Molecular genetic testing enabled the diagnosis of otherwise undiagnosable cases of pyruvate kinase deficiency.

Pediatr Hematol Oncol 2022 Mar 19;39(2):166-173. Epub 2021 Jul 19.

Department of Laboratory Medicine, Donga-A University College of Medicine, Busan, Republic of Korea.

The gold standard for the diagnosis of pyruvate kinase (PK) deficiency, the most frequent red blood cell enzymopathy, is an enzymatic activity assay. However, this assay is rather unreliable in a clinical setting, often leading to misdiagnosis or missed diagnosis. This report presented the cases of two patients diagnosed with PK deficiency using molecular genetic testing, even though conventional laboratory tests, including the PK activity assay, failed to detect any abnormalities. Read More

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Single port robotic splenectomy for pyruvate kinase deficiency in a five-year-old patient, a case report of a surgical first.

Int J Surg Case Rep 2021 Jul 19;84:106122. Epub 2021 Jun 19.

University of Illinois Hospital and Health Sciences System, Division of Pediatric Surgery, Department of Surgery, 840 S. Wood St. Ste 406, Chicago, IL 606112, United States of America. Electronic address:

Introduction: Adoption of robotic surgery in pediatrics has been slow. Robotic surgery within spatially-constrained workspaces in children makes traditional platforms less translatable. Da Vinci's newest single port (SP) robotic platform provides narrow, and deep access, making pediatric robotic surgery more feasible. Read More

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A pyruvate kinase deficiency child with novel PK-LR gene mutations was successfully cured by matched unrelated donor peripheral blood stem cell transplantation.

Pediatr Transplant 2021 Nov 13;25(7):e14078. Epub 2021 Jul 13.

Department of Pediatrics, Sun Yat-sen Memorial Hospital, SunYat-sen University, Guangzhou, China.

Background: Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder caused by a PK-LR gene mutation. Allogeneic hematopoietic cell transplantation (HCT) is an effective cure for PKD. However, the experience of applying HCT in PKD is limited. Read More

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November 2021

Pyruvate kinase deficiency in children.

Pediatr Blood Cancer 2021 09 14;68(9):e29148. Epub 2021 Jun 14.

Dana-Farber/Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts, USA.

Background: Pyruvate kinase deficiency (PKD) is a rare, autosomal recessive red blood cell enzyme disorder, which leads to lifelong hemolytic anemia and associated complications from the disease and its management.

Methods: An international, multicenter registry enrolled 124 individuals younger than 18 years old with molecularly confirmed PKD from 29 centers. Retrospective and prospective clinical data were collected. Read More

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September 2021