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Pediatr Blood Cancer 2021 Jun 14: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

World J Clin Cases 2021 Apr;9(12):2916-2922

Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.

Background: The understanding regarding genetic variation, pathophysiology, and complications associated with pyruvate kinase deficiency (PKD) in red blood cells has been explained largely, and supportive treatment is currently the main management strategy. Etiotropic managements, including transplantation and genome editing, supplying for substitute dugs of the pyruvate kinase, are all under research.

Case Summary: We herein report a 3-year-old boy with severe transfusion-dependent PKD cured by unrelated identical peripheral blood stem cell transplantation (PBSCT). Read More

Br J Haematol 2021 Jun 2;193(5):994-1000. Epub 2021 May 2.

Precision Medicine, King's College Hospital, London, UK.

Pyruvate kinase (PK) deficiency is an autosomal recessive disease caused by mutations in the PKLR gene, which reduce erythrocyte PK enzyme activity and result in decreased energy synthesis in red cells, causing haemolytic anaemia. 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. For our laboratory, the reference range was set by Beutler et al. Read More

Clin Biochem 2021 May 23;91:26-30. Epub 2021 Feb 23.

Servicio de Hematología-Oncología, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Combate de los Pozos 1881, (C1245AAM) Buenos Aires, Argentina. Electronic address:

Background: Pyruvate kinase deficiency (PKD) is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. The disease shows a marked variability in clinical expression. We studied the molecular features of nine unrelated Argentinian patients with congenital hemolytic anemia associated with erythrocyte pyruvate kinase deficiency. Read More

Front Physiol 2020 20;11:609103. Epub 2021 Jan 20.

Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Pyruvate kinase deficiency (PKD) is a rare congenital hemolytic anemia caused by mutations in the gene. Here, we review pathophysiological aspects of PKD, focusing on the interplay between pyruvate kinase (PK)-activity and reticulocyte maturation in the light of ferroptosis, an iron-dependent process of regulated cell death, and in particular its key player glutathione peroxidase 4 (GPX4). GPX4 plays an important role in mitophagy, the key step of peripheral reticulocyte maturation and GPX4 deficiency in reticulocytes results in a failure to fully mature. Read More

Med Clin (Barc) 2021 Jan 9. Epub 2021 Jan 9.

Servicio de Hematología y Hemoterapia, Hospital Universitario Virgen de la Arrixaca, Murcia, España.

Pyruvate kinase (PK) deficiency is the second most frequent enzymopathy and the most common cause of chronic hereditary non-spherocytic haemolytic anaemia. Its global prevalence is underestimated due to low clinical suspicion of mild cases, associated with difficulties in the performance and interpretation of PK enzymatic activity assays. With the advent of next generation sequencing techniques, a better diagnostic approach is achieved. Read More

Eur J Haematol 2021 Apr 24;106(4):484-492. Epub 2021 Jan 24.

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

Objectives: Pyruvate kinase (PK) deficiency is caused by PKLR gene mutations, leading to defective red blood cell glycolysis and hemolytic anemia. Rates of comorbidities and complications by transfusion history and relative to the general population remain poorly quantified.

Methods: Data for patients aged ≥ 18 years with two confirmed PKLR mutations were obtained from the PK deficiency Natural History Study (NCT02053480). Read More

Paediatr Anaesth 2021 Apr 18;31(4):499-500. Epub 2021 Jan 18.

Division of Anesthesiology, Seattle Children's Hospital, Seattle, WA, USA.

Pyruvate dehydrogenase complex deficiency (PDCD) is a rare X-linked disorder that affects glucose metabolism. There are several case reports describing the anesthetic management of patients with PDCD. This is the first case report to describe the anesthetic management of a PDCD patient requiring spontaneous ventilation using dexmedetomidine and ketamine. Read More

Mol Ther Methods Clin Dev 2020 Dec 15;19:426-437. Epub 2020 Oct 15.

Cell Differentiation and Cytometry Unit. 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.

The development of advanced gene and cell therapies for the treatment of genetic diseases requires reliable animal and cellular models to test their efficacy. Moreover, the availability of the target human primary cells of these therapies is reduced in many diseases. The development of endonucleases that can cut into specific sites of the cell genome, as well as the repair of the generated break by non-homologous end-joining, results in a variety of outcomes, insertions, deletions, and inversions that can induce the disruption of any specific gene. Read More

Front Genet 2020 28;11:560248. Epub 2020 Oct 28.

Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.

Background: Red cell pyruvate kinase deficiency (PKD) is a defect of glycolysis causing congenital non-spherocytic hemolytic anemia. PKD is transmitted as an autosomal recessive trait. The clinical features of PKD are highly variable, from mild to life-threatening anemia which can lead to death in the neonatal period. Read More

Haematologica 2020 09 10;Online ahead of print. Epub 2020 Sep 10.

Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht.

The diagnostic evaluation and clinical characterization of rare hereditary anemia (RHA) is to date still challenging. In particular, there is little knowledge on the broad metabolic impact of many of the molecular defects underlying RHA. In this study we explored the potential of untargeted metabolomics to diagnose a relatively common type of RHA: Pyruvate Kinase Deficiency (PKD). Read More

Haematologica 2020 09 1;105(9):2229-2239. Epub 2020 Sep 1.

Dana/Farber Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.

Pyruvate kinase deficiency (PKD) is the most common cause of chronic hereditary non-spherocytic hemolytic anemia and results in a broad spectrum of disease. The diagnosis of PKD requires a high index of suspicion and judicious use of laboratory tests that may not always be informative, including pyruvate kinase enzyme assay and genetic analysis of the PKLR gene. A significant minority of patients with PKD have occult mutations in non-coding regions of PKLR which are missed on standard genetic tests. Read More

Haematologica 2020 09 1;105(9):2218-2228. Epub 2020 Sep 1.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, UOC Ematologia, UOS Fisiopatologia delle Anemie, Milan, Italy.

Red cell pyruvate kinase (PK) deficiency is the most common glycolytic defect associated with congenital non-spherocytic hemolytic anemia. The disease, transmitted as an autosomal recessive trait, is caused by mutations in the PKLR gene and is characterized by molecular and clinical heterogeneity; anemia ranges from mild or fully compensated hemolysis to life-threatening forms necessitating neonatal exchange transfusions and/or subsequent regular transfusion support; complications include gallstones, pulmonary hypertension, extramedullary hematopoiesis and iron overload. Since identification of the first pathogenic variants responsible for PK deficiency in 1991, more than 300 different variants have been reported, and the study of molecular mechanisms and the existence of genotype-phenotype correlations have been investigated in-depth. Read More

Mol Biol Rep 2020 Oct 24;47(10):8311-8315. Epub 2020 Sep 24.

Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Pyruvate kinase deficiency (PKD) is the most common glycolytic defect leading to chronic nonspherocytic hemolytic anemia (CNSHA). Clinical manifestations of PKD reflect the symptoms and complications of the chronic hemolysis, including anemia, jaundice, bilirubin gallstones due to hyperbilirubinemia, splenomegaly and iron overload. In this study, we report the finding of a 5-months-old Turkish male newborn with moderate CNSHA and PKD. Read More

J Korean Med Sci 2020 Aug 24;35(33):e279. Epub 2020 Aug 24.

Department of Pediatrics, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.

Background: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. Read More

Blood 2020 08;136(6):770

Boston Children's Hospital.

Blood 2020 09;136(11):1241-1249

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

Pyruvate kinase deficiency (PKD) is an autosomal-recessive enzyme defect of the glycolytic pathway that causes congenital nonspherocytic hemolytic anemia. The diagnosis and management of patients with PKD can be challenging due to difficulties in the diagnostic evaluation and the heterogeneity of clinical manifestations, ranging from fetal hydrops and symptomatic anemia requiring lifelong transfusions to fully compensated hemolysis. Current treatment approaches are supportive and include transfusions, splenectomy, and chelation. Read More

Front Immunol 2020 23;11:1309. Epub 2020 Jun 23.

UOS Fisiopatologia delle Anemie, UOC Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Congenital hemolytic anemias (CHAs) are a heterogeneous group of rare hereditary conditions including defects of erythrocyte membrane proteins, red cell enzymes, and disorders due to defective erythropoiesis. They are characterized by variable degree of anemia, chronic extravascular hemolysis, reduced erythrocyte life span, splenomegaly, jaundice, biliary lithiasis, and iron overload. Although few data are reported on the role of the immune system in CHAs, several immune-mediated mechanisms may be involved in the pathogenesis of these rare diseases. Read More

Br J Haematol 2020 08 5;190(4):e250-e255. Epub 2020 Jul 5.

School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, BS8 1TD, UK.

Am J Hematol 2020 Jul 3. Epub 2020 Jul 3.

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

J Pediatr Hematol Oncol 2021 05;43(4):e605-e607

Comprehensive Transplant Center, The Ohio State University Wexner Medical Center, Columbus, OH.

We present the case of a successful liver transplant in a young adult patient with cholestasis and cirrhosis secondary to severe pyruvate kinase (PK) deficiency. Liver transplant resulted in resolution of liver dysfunction, decreased need for blood transfusions and eligibility for bone marrow transplantation. This case represents the third reported patient in the literature with severe PK deficiency who successfully underwent liver transplant as a result of profound cholestasis and liver failure. Read More

Int J Lab Hematol 2020 Jun;42 Suppl 1:107-112

University of Utah-Pathology, Salt Lake City, Utah.

Anemia is a major health burden worldwide and affects approximately one-third of world's population. It is not a diagnosis; it is a manifestation of an underlying pathophysiology leading to either decreased hemoglobin (Hb), hematocrit (Hct), or red blood cells (RBCs). Iron deficiency anemia is still the most common cause of anemia worldwide. Read More

Hematol Rep 2020 May 15;12(1):8305. Epub 2020 May 15.

Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.

Pyruvate kinase deficiency (PKD) is the rare glycolytic enzyme defect causing hemolytic anemia. Treatments are mainly red cell transfusion and/or splenectomy, leading to iron overload. Allogeneic bone marrow transplantation (BMT) is alternatively curative treatment for severe PKD. Read More

Br J Haematol 2021 Mar 28;192(6):1092-1096. Epub 2020 May 28.

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

Diagnosis of pyruvate kinase deficiency (PKD), the most common cause of hereditary non-spherocytic haemolytic anaemia, remains challenging in routine practice and no biomarkers for clinical severity have been characterised. This prospective study enrolled 41 patients with molecularly confirmed PKD from nine North American centres to evaluate the diagnostic sensitivity of pyruvate kinase (PK) enzyme activity and PK:hexokinase (HK) enzyme activity ratio, and evaluate the erythrocyte PK (PK-R) protein level and erythrocyte metabolites as biomarkers for clinical severity. In this population not transfused for ≥90 days before sampling, the diagnostic sensitivity of the PK enzyme assay was 90% [95% confidence interval (CI) 77-97%], whereas the PK:HK ratio sensitivity was 98% (95% CI 87-100%). Read More

J Appl Lab Med 2020 01;5(1):54-61

ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT.

Background: Pyruvate kinase (PK) deficiency is the most common cause of nonspherocytic hemolytic anemia owing to defective glycolysis. This study developed and validated an automated method to measure PK activity in red blood cells (RBCs).

Methods: PK catalyzes the reaction of phosphoenolpyruvate with ADP to form pyruvate and ATP. Read More

Br J Haematol 2020 05 10;189(4):635-639. Epub 2020 May 10.

Guys and St Thomas's NHS Trust, London, UK.

With the developing COVID-19 pandemic, patients with inherited anaemias require specific advice regarding isolation and changes to usual treatment schedules. The National Haemoglobinopathy Panel (NHP) has issued guidance on the care of patients with sickle cell disease, thalassaemia, Diamond Blackfan anaemia (DBA), congenital dyserythropoietic anaemia (CDA), sideroblastic anaemia, pyruvate kinase deficiency and other red cell enzyme and membrane disorders. Cascading of accurate information for clinicians and patients is paramount to preventing adverse outcomes, such as patients who are at increased risk of fulminant bacterial infection due to their condition or its treatment erroneously self-isolating if their fever is mistakenly attributed to a viral cause, delaying potentially life-saving antibiotic therapy. Read More

Eur J Haematol 2020 Aug 23;105(2):173-184. Epub 2020 Jun 23.

Agios Pharmaceuticals Inc., Cambridge, MA, USA.

Objectives: Pyruvate kinase deficiency (PK deficiency) is a rare disorder caused by compound heterozygosity or homozygosity for > 300 mutations in the PKLR gene. To understand PK deficiency prevalence, we conducted a systematic literature review.

Methods: We queried Embase and Medline for peer-reviewed references reporting PK deficiency prevalence/incidence, PKLR mutant allele frequency (MAF) among the general population, or crude results from which these metrics could be derived. Read More

Haematologica 2020 07 9;105(7):e373-e375. Epub 2020 Apr 9.

Danish Center for Hemoglobinopathies, Department of Hematology, Herlev and Gentofte Hospital, Herlev

Sleep Med 2020 05 28;69:100-102. Epub 2020 Jan 28.

Neurology and Sleep Unit, La Luz Clinic, Quironsalud, Madrid, Spain.