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Br J Haematol 2019 Mar 25;184(5):721-734. Epub 2019 Jan 25.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Novel therapies in development have brought a new focus on pyruvate kinase deficiency (PKD), the most common congenital haemolytic anaemia due to a glycolytic enzyme deficiency. With an improved recognition of its clinical presentation and understanding of the diagnostic pathway, more patients are likely to be identified with this anaemia. Complications, including gallstones and non-transfusion-related iron overload, require monitoring for early diagnosis and management. Read More

Intractable Rare Dis Res 2018 Nov;7(4):258-263

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.

Thalassemia and other hemoglobinopathies together with red cell enzymopathies are a common cause of anemia, which can be prevented by population screening and genetic counseling. This study was designed to screen the anemic patients for thalassemia, structural hemoglobin variants and red cell enzymopathies. 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. Read More

Qual Life Res 2019 Feb 19;28(2):399-410. Epub 2018 Nov 19.

Haematology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy.

Purpose: Pyruvate kinase deficiency (PKD) is a rare disease and understanding of its epidemiology and associated burden remains limited. With no current curative therapy, clinical manifestations can be life threatening, clinically managed by maintaining adequate hemoglobin levels through transfusion and subsequent support, but with frequent complications. Treatment goals are to maintain/improve the patient's quality of life. Read More

Am J Hematol 2019 Jan 28;94(1):149-161. Epub 2018 Nov 28.

Department of Clinical Chemistry and Haematology, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Pyruvate kinase deficiency (PKD) is the most common enzyme defect of glycolysis and an important cause of hereditary, nonspherocytic hemolytic anemia. The disease has a worldwide geographical distribution but there are no verified data regarding its frequency. Difficulties in the diagnostic workflow and interpretation of PK enzyme assay likely play a role. Read More

Ann Biol Clin (Paris) 2018 Oct;76(5):493-503

Groupement de coopération sanitaire de Saintonge, Centres hospitaliers de Saintes et Royan, Vaux-sur-mer, France, Service de médecine interne, Centre hospitalier de Royan, Vaux-sur-mer, France.

The most frequent causes of hemolytic anemias are immune or infectious diseases, drug induced hemolysis, thrombotic microangiopathies, hereditary spherocytosis, glucose-6-phosphate dehydrogenase or pyruvate kinase deficiencies, thalassemia's and sickle cell disease. Sometimes no cause is found because a rarer etiology is involved. The goal of this review is to remember some unfrequent constitutional or acquired causes and to point out difficulties to avoid wrong interpretations of analysis results. Read More

Haematologica 2019 Feb 13;104(2):e51-e53. Epub 2018 Sep 13.

Dana-Farber Boston Children's Cancer and Blood Disorder Center, Boston, MA, USA

Int J Lab Hematol 2018 Dec 5;40(6):697-703. Epub 2018 Sep 5.

Department of Biological Hematology, Rouen University Hospital, Rouen, France.

Introduction: Development of additional parameters for complete blood count has emerged in recent hematology analyzers, leading to many publications. However, few studies have been conducted on advanced RBC parameters and hemolytic anemias. We investigated the interest of Sysmex unique parameters, MicroR and HypoHe, as well as the immature fraction of reticulocytes (IRF) in combination with complete blood and reticulocyte count, for screening hereditary spherocytosis (HS) and pyruvate kinase deficiency. Read More

Br J Haematol 2018 Sep 5. Epub 2018 Sep 5.

Van Creveldkliniek, University Medical Centre Utrecht, Utrecht, Netherlands.

Clin Pharmacol Drug Dev 2019 Feb 9;8(2):246-259. Epub 2018 Aug 9.

Agios Pharmaceuticals, Inc., Cambridge, MA, USA.

Pyruvate kinase deficiency is a chronic hemolytic anemia caused by mutations in PK-R, a key glycolytic enzyme in erythrocytes. These 2 phase 1 randomized, placebo-controlled, double-blind healthy-volunteer studies assessed the safety, tolerability, and pharmacokinetics/pharmacodynamics of AG-348, a first-in-class allosteric PK-R activator. Twelve sequential cohorts were randomized 2:6 to receive oral placebo or AG-348, respectively, as a single dose (30-2500 mg) in the single-ascending-dose (SAD) study (ClinicalTrials. Read More

J Pediatr Hematol Oncol 2019 Jan;41(1):e1-e2

Division of Pediatric Hematology, Dr. Behçet Uz Children's Hospital, Izmir, Turkey.

Pyruvate kinase deficiency (PKD) is the most common glycolytic defect leading to hemolytic anemia. PKD is caused by the mutations in the PKLR gene; however, the detection of a decreased PK activity should be first measured for rapid diagnosis. We report here the case of a 1-year-old girl with mild hemolysis and PKD. Read More

Zhonghua Nei Ke Za Zhi 2018 Jul;57(7):511-513

Institute of Hematology and Blood Disease Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, State Key Laboratory of Experimental Hematology, Tianjin 300020, China.

Clinical data of 19 patients with congenital pyruvate kinase deficiency were analyzed. Insufficient pyruvate kinase confirmed the diagnosis. Laboratory parameters of hemolysis were summarized. Read More

Eur J Haematol 2018 Dec 28;101(6):758-765. Epub 2018 Sep 28.

Division of Hematology/Oncology, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.

Objectives: This study explored how signs and symptoms of pyruvate kinase (PK) deficiency, a rare hemolytic anemia caused by mutations in the PKLR gene, impacts patients' health-related quality of life (HRQoL).

Methods: Interviews with 21 adults with PK deficiency in the United States, Netherlands, and Germany were conducted. Participants were asked to describe signs, symptoms, and impacts of the disease on their daily lives. Read More

Cureus 2018 Apr 13;10(4):e2478. Epub 2018 Apr 13.

Department of Pediatrics, Shanghai Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, CHN.

Congenital non-spherocytic hemolytic anemia (CNSHA) is a rare autosomal recessive condition that presents as a congenital hemolytic anemia. The absence of vital enzymes required for glycolysis such as homozygous glucose phosphate isomerase (GPI) and red blood cell (RBC) nucleotide metabolism predisposes the RBCs to hemolysis. No spherocytosis is seen on peripheral smear as well as no signs of immune-mediated destruction of RBCs. Read More

Pediatr Clin North Am 2018 06;65(3):579-595

Department of Pediatric Hematology/Oncology, Lucile Packard Children's Hospital, Stanford University School of Medicine, 1000 Welch Road # 300, Palo Alto, CA 94304, USA.

Mature red blood cells are reliant on the glycolytic pathway for energy production and the hexose monophosphate shunt for cell protection from oxidative insults. The most common red blood cell enzyme disorders are characterized by hemolysis but with wide clinical variability. Glucose-6-phosphate dehydrogenase deficiency is the most common red cell enzyme disorder worldwide. Read More

Eur J Haematol 2018 Sep 25;101(3):297-304. Epub 2018 Jun 25.

Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Background: Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes. Read More

Pediatrics 2018 Apr;141(Suppl 5):S385-S389

Division of Gastroenterology, Hepatology, and Nutrition, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada;

Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic chronic hemolytic anemia, and patients normally present with mild to severe anemia, unconjugated hyperbilirubinemia, and splenomegaly. Only a few reports of PKD have documented its association with severe, progressive liver failure. In all those cases, the patients died before liver transplant (LT) or immediately after transplant. Read More

Blood 2018 May 16;131(20):2183-2192. Epub 2018 Mar 16.

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.

An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity. Read More

Rev Bras Hematol Hemoter 2018 Jan - Mar;40(1):5-11. Epub 2017 Nov 26.

Centro de Hematologia e Hemoterapia da Universidade Estadual de Campinas (HEMOCENTRO/UNICAMP), Campinas, SP, Brazil; Departamento de Medicina Interna da Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil. Electronic address:

Background: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase-deficient patients and the genotype-phenotype correlations. Read More

Rev Bras Hematol Hemoter 2018 Jan - Mar;40(1):1-2. Epub 2017 Dec 6.

Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP), São Paulo, SP, Brazil. Electronic address:

Hemoglobin 2018 Jan 8;42(1):43-46. Epub 2018 Feb 8.

a Department of Haematogenetics , National Institute of Immunohaematology, Indian Council of Medical Research , Mumbai , India.

Hemoglobinopathies are a group of inherited single gene disorders. There are reports on hemoglobin (Hb) variants identified in the tribal and non-tribal populations of Tripura State in northeastern India. This study aimed to determine the spectrum of hemoglobinopathies and enzymopathies by newborn screening in Tripura State and assess the extent of neonatal jaundice. Read More

Pediatr Transplant 2018 03 18;22(2). Epub 2018 Jan 18.

Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Thalassemia Research, Nanning, Guangxi Province, China.

This study's purposes were to diagnose intractable hemolytic anemia and to provide guiding treatment for the affected family members. We performed NGS in a panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia and her parents. We confirmed the diagnosis of pyruvate kinase deficiency, identified a novel homozygous mutation of the PKLR gene (NM_000298: exon 6: c. Read More

J Pediatr Hematol Oncol 2018 Oct;40(7):e458-e460

Department of Pediatric Hematology and Oncology, University of Health Sciences, Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital, Ankara, Turkey.

Pyruvate kinase (PK) deficiency is the most common defect of the glycolytic pathway leading to congenital hemolytic anemia. We present the case of an 18-year-old boy with chronic nonspherocytic hemolytic anemia, who had remarkable sensitivity to heat. Moreover, the patient showed clinical impairment in the last year. Read More

Hum Mutat 2018 03 11;39(3):389-393. Epub 2018 Jan 11.

Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Pyruvate kinase deficiency (PKD) is the most frequent red blood cell enzyme abnormality of the glycolytic pathway and the most common cause of hereditary nonspherocytic hemolytic anemia. Over 250 PKLR-gene mutations have been described, including missense/nonsense, splicing and regulatory mutations, small insertions, small and gross deletions, causing PKD and hemolytic anemia of variable severity. Alu retrotransposons are the most abundant mobile DNA sequences in the human genome, contributing to almost 11% of its mass. Read More

Blood 2017 12;130(26):2906

Temple University Hospital.

Haematologica 2018 02 14;103(2):e82-e86. Epub 2017 Dec 14.

Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht University, the Netherlands

Int J Lab Hematol 2018 Apr 1;40(2):159-168. Epub 2017 Nov 1.

Result Laboratory, Albert Schweitzer Hospital, Dordrecht, The Netherlands.

Introduction: Evaluation of red blood cell (RBC) morphology is an important first step in the differential diagnosis of hereditary hemolytic anemia. It is, however, labor intensive, expensive, and prone to subjectivity. To improve and standardize the analysis of RBC morphology as a screening tool in the diagnosis of hereditary hemolytic anemia, we studied its automated analysis by digital microscopy (DM). Read More

Zhonghua Xue Ye Xue Za Zhi 2017 Jul;38(7):631-633

Institute of Hematology & Hospital of Blood Diseases, CAMS & PUMC, Tianjin 300020, China.

Blood 2017 09 31;130(11):1347-1356. Epub 2017 Jul 31.

Agios Pharmaceuticals, Inc., Cambridge, MA; and.

Pyruvate kinase (PK) deficiency is a rare genetic disease that causes chronic hemolytic anemia. There are currently no targeted therapies for PK deficiency. Here, we describe the identification and characterization of AG-348, an allosteric activator of PK that is currently in clinical trials for the treatment of PK deficiency. Read More

PLoS One 2017 18;12(5):e0177818. Epub 2017 May 18.

Biochemistry Department, McGill University, Montreal, Quebec, Canada.

Pyruvate kinase (PKLR) deficiency protects mice and humans against blood-stage malaria. Although mouse strain AcB62 carries a malaria-protective PklrI90N genetic mutation, it is phenotypically susceptible to blood stage malaria induced by infection with Plasmodium chabaudi AS, suggesting a genetic modifier of the PklrI90N protective effect. Linkage analysis in a F2 cross between AcB62 (PklrI90N) and another PK deficient strain CBA/Pk (PklrG338D) maps this modifier (designated Char10) to chromosome 9 (LOD = 10. Read More

An Pediatr (Barc) 2018 Feb 25;88(2):106-107. Epub 2017 Apr 25.

Servicio de Hemato-Oncología Pediátrica, Hospital Infantil Universitario Niño Jesús, Madrid, España.

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

Eur J Haematol 2017 Jun 12;98(6):584-589. Epub 2017 Apr 12.

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

Clin Chim Acta 2017 May 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

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

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

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

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

J Cardiothorac Vasc Anesth 2017 02 23;31(1):262-265. Epub 2016 Mar 23.

Department of Anaesthesia, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, India.

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

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

Am J Med Genet A 2016 09 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

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.

Blood 2016 05;127(21):2505

Mol Ther 2016 08 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

Pediatr Blood Cancer 2016 May 2;63(5):771-2. Epub 2016 Feb 2.

Departments of Pediatrics and Pathology, Stanford University School of Medicine, Stanford, California.

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

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

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

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

Stem Cell Reports 2015 Dec 5;5(6):1053-1066. 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