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    442 results match your criteria Pyruvate Kinase Deficiency

    1 OF 9

    Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families.
    Case Rep Hematol 2017 6;2017:2769570. Epub 2017 Mar 6.
    U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
    Hereditary xerocytosis (HX) is a rare disorder caused by defects of RBC permeability, associated with haemolytic anaemia of variable degree and iron overload. It is sometimes misdiagnosed as hereditary spherocytosis or other congenital haemolytic anaemia. Splenectomy is contraindicated due to increased risk of thromboembolic complications. Read More

    Residual pyruvate kinase activity in PKLR-deficient erythroid precursors of a patient suffering from severe haemolytic anaemia.
    Eur J Haematol 2017 Mar 10. Epub 2017 Mar 10.
    Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, University of Amsterdam, Amsterdam, The Netherlands.
    Objective: Here, we present a 7-year-old patient suffering from severe haemolytic anaemia. The most common cause of chronic hereditary non-spherocytic haemolytic anaemia is red blood cell pyruvate kinase (PK-R) deficiency. Because red blood cells rely solely on glycolysis to generate ATP, PK-R deficiency can severely impact energy supply and cause reduction in red blood cell lifespan. Read More

    Next-generation sequencing unravels homozygous mutation in glucose-6-phosphate isomerase, GPIc.1040G>A (p.Arg347His) causing hemolysis in an Indian infant.
    Clin Chim Acta 2017 Feb 20;468:81-84. Epub 2017 Feb 20.
    Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address:
    Introduction: Inherited anemias diagnostic workup requires a step-wise algorithm. Causal genes implicated in congenital hemolytic anemia are numerous, making a gene-by-gene approach by Sanger sequencing time consuming, expensive and labour intensive. Targeted resequencing can be of great use in explaining these cases. Read More

    Congenital Hemolytic Anemia.
    Med Clin North Am 2017 Mar 8;101(2):361-374. Epub 2016 Dec 8.
    Department of Pediatrics, Division of Pediatric Hematology/Oncology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code CDRCP, Portland, OR 97239, USA. Electronic address:
    Red blood cell (RBC) destruction can be secondary to intrinsic disorders of the RBC or to extrinsic causes. In the congenital hemolytic anemias, intrinsic RBC enzyme, RBC membrane, and hemoglobin disorders result in hemolysis. The typical clinical presentation is a patient with pallor, anemia, jaundice, and often splenomegaly. Read More

    Molecular basis of pyruvate kinase deficiency among Tunisians: description of new mutations affecting coding and noncoding regions in the PKLR gene.
    Int J Lab Hematol 2017 Apr 30;39(2):223-231. Epub 2017 Jan 30.
    Laboratoire d'Hématologie Moléculaire et Cellulaire, Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis, Tunisia.
    Introduction: Pyruvate kinase (PK) deficiency is one of the most common hereditary nonspherocytic hemolytic anemias worldwide with clinical manifestations ranging from mild to severe hemolysis. However, investigation of this enzymopathy is lacking in Tunisia. We report here a pioneer investigation of PK deficiency among Tunisian cases referred to our laboratory for biological analysis of unknown cause of hemolytic anemia. Read More

    Red cell pyruvate kinase deficiency in Spain: A study of 15 cases.
    Med Clin (Barc) 2017 Jan 19;148(1):23-27. Epub 2016 Nov 19.
    Unidad de Eritropatología, Hospital Clínic de Barcelona, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España.
    Background And Objective: Pyruvate kinase deficiency (PKD) is a rare, inherited disease causing chronic hemolysis and anemia of varying intensity. The genetic heterogeneity of PKD is high and, to this day, over 240 different mutations have been identified.

    Patients And Methods: 15 unrelated patients affected by PKD have been studied. Read More

    Plesiomonas shigelloides Septic Shock Leading to Death of Postsplenectomy Patient with Pyruvate Kinase Deficiency and Hemochromatosis.
    Case Rep Infect Dis 2016 17;2016:1538501. Epub 2016 Aug 17.
    Department of Medicine, Buffalo Mercy Hospital, University at Buffalo, Buffalo, NY 14220, USA.
    Although Plesiomonas shigelloides, a water-borne bacterium of the Enterobacteriaceae family, usually causes self-limiting gastroenteritis with diarrhea, several cases of sepsis have been reported. We report the case of a 43-year-old male patient with hemochromatosis, pyruvate kinase deficiency, and asplenia via splenectomy who developed septic shock caused by P. shigelloides complicated by respiratory failure, renal failure, liver failure, and disseminated intravascular coagulation. Read More

    Cord blood transplantation in a young child with pyruvate kinase deficiency.
    Pediatr Int 2016 Jul 8;58(7):634-6. Epub 2016 Mar 8.
    Department of Pediatrics and Child Neurology, Oita University Faculty of Medicine, Hasama, Yufu, Oita, Japan.
    Unrelated cord blood transplantation (CBT) was performed for the treatment of pyruvate kinase (PK) deficiency in a female pediatric patient at the age of 1 year 7 months, who had been in severe and frequent transfusion-dependent hemolytic anemia, despite red blood cell (RBC) PK activity 5.52 IU/gHb. pyruvate kinase-liver and RBC (PK-LR) had a compound heterozygous mutation located on exon 8: c. Read More

    A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias.
    Br J Haematol 2016 Oct 19;175(2):318-330. Epub 2016 Jul 19.
    BRC Blood Theme and BRC/NHS Translational Molecular Diagnostics Centre, John Radcliffe Hospital, Oxford, UK.
    Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. Read More

    Siblings with severe pyruvate kinase deficiency and a complex genotype.
    Am J Med Genet A 2016 Sep 29;170(9):2449-52. Epub 2016 Jun 29.
    ARUP Laboratories, Salt Lake City, Utah.
    Siblings presented as neonates with severe jaundice and transfusion-dependent hemolytic anemia. Next-generation sequencing revealed both to have three heterozygous mutations in the gene encoding erythrocyte pyruvate kinase (PKLR), plus a heterozygous splice mutation in the beta-spectrin gene (SPTB). In addition, both have a different 5th mutation in a gene encoding other erythrocyte membrane proteins. Read More

    Congenital dyserythropoietic anemia associated to a GATA1 mutation aggravated by pyruvate kinase deficiency.
    Ann Hematol 2016 Sep 24;95(9):1551-3. Epub 2016 Jun 24.
    Serviço de Hematologia Clínica, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Avenida Afonso Romão, 3000-602, Coimbra, Portugal.

    Safe and Efficient Gene Therapy for Pyruvate Kinase Deficiency.
    Mol Ther 2016 Aug 3;24(7):1187-98. Epub 2016 May 3.
    Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) - Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
    Pyruvate kinase deficiency (PKD) is a monogenic metabolic disease caused by mutations in the PKLR gene that leads to hemolytic anemia of variable symptomatology and that can be fatal during the neonatal period. PKD recessive inheritance trait and its curative treatment by allogeneic bone marrow transplantation provide an ideal scenario for developing gene therapy approaches. Here, we provide a preclinical gene therapy for PKD based on a lentiviral vector harboring the hPGK eukaryotic promoter that drives the expression of the PKLR cDNA. Read More

    Red blood cell PK deficiency: An update of PK-LR gene mutation database.
    Blood Cells Mol Dis 2016 Mar 12;57:100-9. Epub 2016 Jan 12.
    Laboratory of Clinical Molecular and Personalized Diagnostics, Department of Laboratory Medicine, "A Gemelli" Hospital, Catholic University, Largo Agostino Gemelli 8, Roma, Italy.
    Pyruvate kinase (PK) deficiency is known as being the most common cause of chronic nonspherocytic hemolytic anemia (CNSHA). Clinical PK deficiency is transmitted as an autosomal recessive trait, that can segregate neither in homozygous or in a compound heterozygous modality, respectively. Two PK genes are present in mammals: the pyruvate kinase liver and red blood cells (PK-LR) and the pyruvate kinase muscle (PK-M), of which only the first encodes for the isoenzymes normally expressed in the red blood cells (R-type) and in the liver (L-type). Read More

    [Analysis and prenatal diagnosis of PKLR gene mutations in a family with pyruvate kinase deficiency].
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2016 Feb;33(1):53-6
    Department of Hematology, Bethune International Peace Hospital of PLA, Shijiazhuang, Hebei 050082, China.
    Objective: To evaluate the feasibility of genetic and prenatal diagnosis for a family affected with pyruvate kinase deficiency (PKD).

    Methods: Targeted sequence capture and high-throughput sequencing technology was used to detect the exons and exon-intron boundaries of the PKLR gene in a clinically suspected PKD patient. Meanwhile, the genotype of the pedigree was validated by Sanger sequencing. Read More

    The Diagnostic Utility of Single Long Contiguous Stretches of Homozygosity in Patients without Parental Consanguinity.
    Mol Syndromol 2015 Sep 15;6(3):135-40. Epub 2015 Aug 15.
    Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Department of Pediatrics, University of Tartu, Tartu, Estonia.
    We present data from our clinical department's experience with chromosomal microarray analysis (CMA) regarding the diagnostic utility of 1 or 2 long contiguous stretches of homozygosity (LCSHs) in an outbred population. The study group consisted of 2,110 consecutive patients from 2011 to 2014 for whom CMA was performed. The minimum cut-off size for defining a homozygous stretch was 5 Mb. Read More

    Two Novel Missense Mutations and a 5bp Deletion in the Erythroid-Specific Promoter of the PKLR Gene in Two Unrelated Patients With Pyruvate Kinase Deficient Transfusion-Dependent Chronic Nonspherocytic Hemolytic Anemia.
    Pediatr Blood Cancer 2016 May 5;63(5):914-6. Epub 2016 Jan 5.
    St. Anna Children's Hospital, Department of Pediatrics, Medical University Vienna.
    We report two children with severe chronic hemolytic anemia, the cause of which was difficult to establish because of transfusion dependency. Reduced erythrocyte pyruvate kinase activity in their asymptomatic parents provided the diagnostic clues for mutation screening of the PKLR gene and revealed that one child was a compound heterozygote of a novel paternally derived 5-bp deletion in the promoter region (c.-88_-84delTCTCT) and a maternally derived missense mutation in exon nine (c. Read More

    Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells.
    Stem Cell Reports 2015 Dec 5;5(6):1053-66. Epub 2015 Nov 5.
    Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid 28040, Spain; Advanced Therapies Mixed Unit, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid 28040, Spain. Electronic address:
    Pyruvate kinase deficiency (PKD) is a rare erythroid metabolic disease caused by mutations in the PKLR gene. Erythrocytes from PKD patients show an energetic imbalance causing chronic non-spherocytic hemolytic anemia, as pyruvate kinase defects impair ATP production in erythrocytes. We generated PKD induced pluripotent stem cells (PKDiPSCs) from peripheral blood mononuclear cells (PB-MNCs) of PKD patients by non-integrative Sendai viral vectors. Read More

    [A PKLR Gene Novel Complex Mutation in Erythrocyte Pyruvate Kinase Deficiency Detected by Targeted Sequence Capture and Next Generation Sequencing].
    Zhongguo Shi Yan Xue Ye Xue Za Zhi 2015 Oct;23(5):1464-8
    Department of Hematology, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang 050082, Hebei Province, China.
    Objective: To explore the molecular mechanism of erythrocyte pyruvate kinase deficiency (PKD).

    Methods: Targeted sequence capture and next-generation sequencing (NGS) were used to detect the regions of exon and exon-intron boundarie of PKLR gene in a clinical suspected PKD patient. The protein function of mutant gene was forecasted by the SIFT and PolyPhen-2 databank, after the mutation of PKLR gene in the patient was detected by the NGS technology, its genotype was confirmed by Sanger sequencing. Read More

    Cholestasis and Hepatic Failure in a Neonate: A Case Report of Severe Pyruvate Kinase Deficiency.
    Pediatrics 2015 Nov 12;136(5):e1366-8. Epub 2015 Oct 12.
    Division of Gastroenterology and Hepatology, Department of Pediatrics, Sainte Justine Hospital, Montréal, Québec, Canada.
    Unexpected severe cholestasis is part of the presentation in some neonates with hemolytic anemia but is usually self-resolving. Here we report the case of a neonate with pyruvate kinase deficiency (PKD) who presented severe hemolytic anemia at birth, characterized by a rapidly progressive and severe cholestasis with normal γ-glutamyl transpeptidase level associated with hepatic failure. After an extensive investigation to rule out contributing conditions explaining the severity of this patient's clinical presentation, PKD has remained the sole identified etiology. Read More


    Anemia in the Neonate: The Differential Diagnosis and Treatment.
    Pediatr Ann 2015 Jul;44(7):e159-63
    Anemia is a common problem in the neonatal period. Presenting symptoms may suggest numerous possible diagnoses ranging from anemia seen as a normal part of development to anemia due to critical pathology. An illustrative case is presented to highlight the appropriate evaluation of the neonate with significant anemia. Read More

    Erythrocyte pyruvate kinase deficiency: 2015 status report.
    Am J Hematol 2015 Sep 14;90(9):825-30. Epub 2015 Aug 14.
    Department, of Pediatrics and Pathology, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California.
    Over the last several decades, our understanding of the genetic variation, pathophysiology, and complications of the hemolytic anemia associated with red cell pyruvate kinase deficiency (PKD) has expanded. Nonetheless, there remain significant gaps in our knowledge with regard to clinical care and monitoring. Treatment remains supportive with phototherapy and/or exchange transfusion in the newborn period, regular or intermittent red cell transfusions in children and adults, and splenectomy to decrease transfusion requirements and/or anemia related symptoms. Read More

    Molecular Analyses of Pyruvate Kinase Deficient Turkish Patients from a Single Center.
    Pediatr Hematol Oncol 2015 5;32(5):354-61. Epub 2015 May 5.
    Division of Pediatric Hematology, Department of Pediatrics, Hacettepe University , Ankara , Turkey.
    Erythrocyte pyruvate kinase deficiency is one of the most common causes of hereditary non-spherocytic hemolytic anemias. We investigated molecular alterations responsible for erythrocyte pyruvate kinase enzyme deficiency in four patients of the three unrelated Turkish families available from the pool of 12 patients diagnosed as having pyruvate kinase deficiency in one center. One novel missense mutation located at cDNA nt 1623 G→C (Lys541Asn), and three previously described mutations at 1456 C→T (Arg486Trp), 1528 C→T (Arg510End), and 1675 C→G (Arg559Gly) were found to be associated with erythrocyte pyruvate kinase deficiency. Read More

    Co-inheritance of G6PD and PK deficiencies in a neonate carrying a Novel UGT1A1 genotype associated to Crigler-Najjar type II syndrome.
    Pediatr Blood Cancer 2015 Sep 27;62(9):1680-1. Epub 2015 Mar 27.
    Department of Laboratory Medicine, Laboratory of Clinical Molecular and Personalized Diagnostics, Roma, Italy.

    Western immunoblotting as a new tool for investigating direct antiglobulin test-negative autoimmune hemolytic anemias.
    Transfusion 2015 Jun 24;55(6 Pt 2):1529-37. Epub 2015 Mar 24.
    Department of Laboratory Medicine and Pathobiology, University of Toronto.
    Background: Direct antiglobulin test-negative (DAT(-)) autoimmune hemolytic anemia, characterized by hemolysis without detectable immunoglobulin or complement on patient red blood cells (RBCs), poses a diagnostic challenge. To select therapy, classification of the hemolysis as immune- or non-immune-mediated is important. We developed a method using Western immunoblot (WB) to classify DAT(-) patients by measuring and comparing levels of RBC immunoglobulin (Ig)G to normal donors. Read More

    Real-time PCR genotyping assay for feline erythrocyte pyruvate kinase deficiency and mutant allele frequency in purebred cats in Japan.
    J Vet Med Sci 2015 Jun 13;77(6):743-6. Epub 2015 Feb 13.
    Laboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Kohrimoto, Kagoshima 890-0065, Japan.
    Erythrocyte pyruvate kinase (PK) deficiency is an inherited glycolytic erythroenzymopathy caused by mutations of the PKLR gene. A causative mutation of the feline PKLR gene was originally identified in Abyssinian and Somali cats in the U.S. Read More

    Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3 deficiency in a family with hereditary spherocytosis.
    Am J Hematol 2015 Mar 24;90(3):E35-9. Epub 2014 Nov 24.
    Laboratory of Red Blood Cell Diagnostics, Department of Blood Cell Research, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands.
    In a family with mild dominant spherocytosis, affected members showed partial band 3 deficiency. The index patient showed more severe clinical symptoms than his relatives, and his red blood cells displayed concomitant low pyruvate kinase activity. We investigated the contribution of partial PK deficiency to the phenotypic expression of mutant band 3 in this family. Read More

    Exploring putative molecular mechanisms of human pyruvate kinase enzyme deficiency and its role in resistance against Plasmodium falciparum malaria.
    Interdiscip Sci 2014 Jun 17;6(2):158-66. Epub 2014 Jun 17.
    Department of Biotechnology, Faculty of Engineering & Technology, Raja Balwant Singh, Engineering Technical Campus, Agra, 283105, U.P., India.
    Malaria is the third most prevalent cause of global mortality and is an interesting case of evolutionary selection. In response to high frequency of malaria infection, several host genetic factors have been selected, such as Hemoglobin variants, Glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase deficiency. Among these popular host genetic factors, deficiency of pyruvate kinase enzyme is one of the most important factor that provide resistance against malaria. Read More

    [Analysis of a pyruvate kinase deficiency consanguineous pedigree caused by Ile314Thr homozygous mutation].
    Zhonghua Xue Ye Xue Za Zhi 2014 Jul;35(7):601-4
    Department of Hematology, Chang Zheng Hospital, The Second Military Medical University, Shanghai 200003, China.
    Objective: To screen potential mutation and explore the underlying mechanism for a consanguineous pedigree featuring pyruvate kinase (PK) deficiency.

    Methods: The red blood cell pyruvate kinase activities of all family members were detected. All the exons and intron-exon boundaries of the PKLR gene for the proband were amplified and analyzed by direct sequencing. Read More

    A previously unknown mutation in the pyruvate kinase gene (PKLR) identified from a neonate with severe jaundice.
    Neonatology 2014 24;106(2):140-2. Epub 2014 Jun 24.
    Department of Pediatrics, Division of Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
    We report a neonate with early and severe hemolytic jaundice and low erythrocyte pyruvate kinase enzymatic activity (<2 U/g hemoglobin, reference interval 9-22). We found her asymptomatic mother to be heterozygous for a novel PKLR mutation (c.1573delT) with an erythrocyte PK activity of 6. Read More

    Causes of hemolysis in neonates with extreme hyperbilirubinemia.
    J Perinatol 2014 Aug 24;34(8):616-9. Epub 2014 Apr 24.
    ARUP Laboratories and the Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
    Objective: We instituted a quality improvement process to enhance our capacity to diagnose genetic hemolytic conditions in neonates with extreme hyperbilirubinemia.

    Study Design: During a 1-year period, whenever the total serum bilirubin (TSB) was >25 mg dl(-1) a special evaluation was performed. If we deemed an erythrocyte membrane defect likely, based on red blood cell morphology, EMA-flow cytometry was performed. Read More

    A novel and a previously described compound heterozygous PKLR gene mutations causing pyruvate kinase deficiency in a Chinese child.
    Fetal Pediatr Pathol 2014 Jun 6;33(3):182-90. Epub 2014 Mar 6.
    Department of Laboratory Medicine, Shanghai Jiaotong University School of Medicine , Shanghai , China.
    Background: Pyruvate kinase deficiency (PKD) is one of the most common enzymatic defects in humans and it is an autosomal recessive disorder causing chronic nonspherocytic hemolytic anemia.

    Methods: A two-year-old male baby with severe hemolytic anemia and low level of pyruvate kinase (PK) activity was enrolled in this study. All exons of PKLR gene and their flanking sequences were amplified from the patient's genomic DNA using PCR. Read More

    Iron status in patients with pyruvate kinase deficiency: neonatal hyperferritinaemia associated with a novel frameshift deletion in the PKLR gene (p.Arg518fs), and low hepcidin to ferritin ratios.
    Br J Haematol 2014 May 18;165(4):556-63. Epub 2014 Feb 18.
    Department of Biology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
    Pyruvate kinase (PK) deficiency is an iron-loading anaemia characterized by chronic haemolysis, ineffective erythropoiesis and a requirement for blood transfusion in most cases. We studied 11 patients from 10 unrelated families and found nine different disease-causing PKLR mutations. Two of these mutations - the point mutation c. Read More

    Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney.
    Pediatr Blood Cancer 2014 Aug 30;61(8):1463-5. Epub 2014 Jan 30.
    Department of Pediatric Hematology and Oncology, University of Texas Medical Branch at Galveston, Galveston, Texas.
    Pyruvate kinase (PK) deficiency is the commonest enzyme deficiency in the glycolytic pathway leading to hemolytic anemia secondary to decreased Adenosine Triphosphate (ATP) synthesis in the red cells. synthesis. PK deficiency due to mutations in the PKLR (1q21) gene leads to highly variable clinical presentation ranging from severe fetal anemia to well compensated anemia in adults. Read More

    Reticulocyte-prone malaria parasites predominantly invade CD71hi immature cells: implications for the development of an in vitro culture for Plasmodium vivax.
    Malar J 2013 Dec 1;12:434. Epub 2013 Dec 1.
    ICREA at Barcelona Centre for International H ealth Research (CRESIB, Hospital Clínic-Universitat de Barcelona)/ISGlobal, Barcelona, Spain.
    Background: The lack of a continuous in vitro culture system for blood stages of malarial parasites with a unique tropism for reticulocytes, such as Plasmodium vivax and the Plasmodium yoelii 17X reticulocyte-prone strain, hinders research in these organisms. The maturation of reticulocytes into erythrocytes is a complex process involving the selective removal of membrane proteins such as the transferrin receptor, CD71. In order to advance in the characterization of infected cells during experimental infections of BALB/c mice with P. Read More

    Reprogramming homing endonuclease specificity through computational design and directed evolution.
    Nucleic Acids Res 2014 Feb 21;42(4):2564-76. Epub 2013 Nov 21.
    Department of Biochemistry, University of Washington, UW Box 357350, 1705 NE Pacific St., Seattle, WA 98195, USA, Graduate Program in Biomolecular Structure and Design, University of Washington, UW Box 357350, 1705 NE Pacific St., Seattle, WA 98195, USA, Graduate Program in Molecular and Cellular Biology, University of Washington, UW Box 357275, 1959 NE Pacific St., Seattle, WA 98195, USA, Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, Imperial College Road, London SW7 2AZ, UK, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB1 3QA, UK, Institute for Systems Biology, 401 Terry Avenue N, Seattle, WA 98109, USA and Howard Hughes Medical Institute, University of Washington, UW Box 357350, 1705 NE Pacific St., Seattle, WA 98195, USA.
    Homing endonucleases (HEs) can be used to induce targeted genome modification to reduce the fitness of pathogen vectors such as the malaria-transmitting Anopheles gambiae and to correct deleterious mutations in genetic diseases. We describe the creation of an extensive set of HE variants with novel DNA cleavage specificities using an integrated experimental and computational approach. Using computational modeling and an improved selection strategy, which optimizes specificity in addition to activity, we engineered an endonuclease to cleave in a gene associated with Anopheles sterility and another to cleave near a mutation that causes pyruvate kinase deficiency. Read More

    Erythrocyte pyruvate kinase deficiency in three West Highland white terriers in Ireland and the UK.
    Ir Vet J 2013 Jul 10;66(1):12. Epub 2013 Jul 10.
    University College Dublin Veterinary Hospital, School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland.
    Erythrocyte pyruvate kinase (PK) deficiency is described for the first time in three apparently unrelated West Highland white terriers (WHWT) from Ireland and the UK. All three dogs were diagnosed with markedly regenerative but persistent anaemia and had been treated for presumed immune-mediated haemolytic anaemia (IMHA) before hereditary erythrocyte PK-deficiency was confirmed by breed-specific DNA mutation analysis. This hereditary erythroenzymopathy causes haemolytic anaemia and affects several canine breeds with varying degrees of severity. Read More

    Molecular and clinical heterogeneity in pyruvate kinase deficiency in India.
    Blood Cells Mol Dis 2013 Oct 14;51(3):133-7. Epub 2013 Jun 14.
    National Institute of Immunohaematology (Indian Council of Medical Research), K.E.M. Hospital Campus, Parel, Mumbai, India.
    We studied the PK-LR gene in 10 unrelated Indian patients with congenital haemolytic anemia associated with erythrocyte pyruvate kinase deficiency. The patients had a variable presentation ranging from a very mild compensated hemolysis to severe anemia. Nine different mutations were detected among the 20 mutated alleles identified: one deletion (c. Read More

    A case of hereditary spherocytosis misdiagnosed as pyruvate kinase deficient hemolytic anemia.
    Clin Lab 2013 ;59(3-4):421-4
    Hematology and Transplantation Unit, Pathophysiology ofAnemia, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
    Background: Hereditary spherocytosis (HS) and pyruvate kinase (PK) deficiency are the most common causes of congenital hemolytic anemia. We describe a case of HS with defective PK activity initially misdiagnosed as PK deficiency.

    Methods: Hematologic investigation, SDS-PAGE analysis of red cell membrane proteins and sequencing of the PKLR gene were performed. Read More

    A case of severe pyruvate kinase deficiency in a primigravida: successful outcome.
    Obstet Med 2013 Jun 3;6(2):90-91. Epub 2013 May 3.
    Consultant Obstetrician, Queen's Hospital, Rom Valley Way, Romford, Essex, RM7 0AG.
    Pyruvate kinase deficiency (PKD) is a rare non-spherocytic type of haemolytic anaemia. During pregnancy, women with severe PKD are at increased risk of infection, thrombosis, hypertension, fetal growth restriction and anaemia. Management of such cases requires close collaboration between a haematologist and an obstetrician. Read More

    [The spleen in non-malignant haematological disorders].
    Ther Umsch 2013 Mar;70(3):157-62
    Abteilung Hämatologie und Hämatologisches Zentrallabor, Luzerner Kantonsspital, Luzern.
    The spleen functions as a filter of the circulating blood, removing aging or abnormal red blood cells, intraerythrocyte inclusions as well as foreign particals. As the spleen is composed of lymphocytic tissue, circulatory elements and mononuclear phagocytic cells it plays an important role in the nonspecific as well as the specific immune response. Additionally, the spleen serves as a reservoir for circulating blood cells, especially platelet sequestration by the spleen is well do cumented. Read More

    Large animal models for foamy virus vector gene therapy.
    Viruses 2012 Dec 7;4(12):3572-88. Epub 2012 Dec 7.
    Department of Pharmaceutical Sciences, Washington State University, 99164-6534, Pullman, WA, USA.
    Foamy virus (FV) vectors have shown great promise for hematopoietic stem cell (HSC) gene therapy. Their ability to efficiently deliver transgenes to multi-lineage long-term repopulating cells in large animal models suggests they will be effective for several human hematopoietic diseases. Here, we review FV vector studies in large animal models, including the use of FV vectors with the mutant O6-methylguanine-DNA methyltransferase, MGMTP140K to increase the number of genetically modified cells after transplantation. Read More

    Erythrocyte pyruvate kinase deficiency mutation identified in multiple breeds of domestic cats.
    BMC Vet Res 2012 Oct 30;8:207. Epub 2012 Oct 30.
    Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
    Background: Erythrocyte pyruvate kinase deficiency (PK deficiency) is an inherited hemolytic anemia that has been documented in the Abyssinian and Somali breeds as well as random bred domestic shorthair cats. The disease results from mutations in PKLR, the gene encoding the regulatory glycolytic enzyme pyruvate kinase (PK). Multiple isozymes are produced by tissue-specific differential processing of PKLR mRNA. Read More

    Pyruvate kinase deficiency in sub-Saharan Africa: identification of a highly frequent missense mutation (G829A;Glu277Lys) and association with malaria.
    PLoS One 2012 17;7(10):e47071. Epub 2012 Oct 17.
    Centro de Malária e outras Doenças Tropicais, Unidade de Parasitologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
    Background: Pyruvate kinase (PK) deficiency, causing hemolytic anemia, has been associated to malaria protection and its prevalence in sub-Saharan Africa is not known so far. This work shows the results of a study undertaken to determine PK deficiency occurrence in some sub-Saharan African countries, as well as finding a prevalent PK variant underlying this deficiency.

    Materials And Methods: Blood samples of individuals from four malaria endemic countries (Mozambique, Angola, Equatorial Guinea and Sao Tome and Principe) were analyzed in order to determine PK deficiency occurrence and detect any possible high frequent PK variant mutation. Read More

    Stem cell selection in vivo using foamy vectors cures canine pyruvate kinase deficiency.
    PLoS One 2012 13;7(9):e45173. Epub 2012 Sep 13.
    Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
    Background: Hematopoietic stem cell (HSC) gene therapy has cured immunodeficiencies including X-linked severe combined immunodeficiency (SCID-X1) and adenine deaminase deficiency (ADA). For these immunodeficiencies corrected cells have a selective advantage in vivo, and low numbers of gene-modified cells are sufficient to provide therapeutic benefit. Strategies to efficiently transduce and/or expand long-term repopulating cells in vivo are needed for treatment of diseases that require higher levels of corrected cells, such as hemoglobinopathies. Read More

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