Pyruvate Kinase Deficiency: Current Challenges and Future Prospects
Bruno Fattizzo,1,2 Francesca Cavallaro,1,2 Anna Paola Maria Luisa Marcello,1 Cristina Vercellati,1 Wilma Barcellini1 1Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 2Department of Oncology and Hemato-Oncology, University of Milan, Milan, ItalyCorrespondence...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-09-01
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| Series: | Journal of Blood Medicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/pyruvate-kinase-deficiency-current-challenges-and-future-prospects-peer-reviewed-fulltext-article-JBM |
| _version_ | 1797999053147996160 |
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| author | Fattizzo B Cavallaro F Marcello APML Vercellati C Barcellini W |
| author_facet | Fattizzo B Cavallaro F Marcello APML Vercellati C Barcellini W |
| author_sort | Fattizzo B |
| collection | DOAJ |
| description | Bruno Fattizzo,1,2 Francesca Cavallaro,1,2 Anna Paola Maria Luisa Marcello,1 Cristina Vercellati,1 Wilma Barcellini1 1Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 2Department of Oncology and Hemato-Oncology, University of Milan, Milan, ItalyCorrespondence: Bruno Fattizzo, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Hematology Unit, Via F. Sforza 35, Milan, 20122, Italy, Tel +39 0255033477, Email bruno.fattizzo@unimi.itAbstract: Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disease marked by chronic hemolytic anemia of various severity and frequent complications including gallstones, splenomegaly, iron overload, and others. Disease phenotype is highly heterogeneous and changes over time with children, adolescents and adult patients displaying different transfusion requirement and rates of complications. The diagnosis relies on the initial clinical suspicion in a patient with chronic hemolysis and exclusion of other more common congenital forms of hemolytic anemias; it is supported by the demonstration of reduced PK enzyme activity, and further confirmed by the detection of (homozygous or compound heterozygous) mutations of PKLR gene. Therapy is mainly supportive, with vitamin supplementation and transfusions (based on symptoms and patient growth rather than on fixed Hb thresholds). Splenectomy is widely performed, although it is less effective than in membrane defects and carries thrombotic and infectious risk. In the last decade, the allosteric PK enzyme activator mitapivat showed dramatic clinical benefit in clinical trials and gene therapy is also being studied to substitute the defective enzyme. In this review, we provide an insight in the current challenges of PKD diagnosis and management and discuss the future application of novel drugs and gene therapy, including a focus on quality of life.Keywords: pyruvate kinase deficiency, splenectomy, mitapivat, gene therapy |
| first_indexed | 2024-04-11T10:58:32Z |
| format | Article |
| id | doaj.art-3cc2e1fa427b4faa9b3a4ac160c4c9aa |
| institution | Directory Open Access Journal |
| issn | 1179-2736 |
| language | English |
| last_indexed | 2024-04-11T10:58:32Z |
| publishDate | 2022-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Blood Medicine |
| spelling | doaj.art-3cc2e1fa427b4faa9b3a4ac160c4c9aa2022-12-22T04:28:43ZengDove Medical PressJournal of Blood Medicine1179-27362022-09-01Volume 1346147177877Pyruvate Kinase Deficiency: Current Challenges and Future ProspectsFattizzo BCavallaro FMarcello APMLVercellati CBarcellini WBruno Fattizzo,1,2 Francesca Cavallaro,1,2 Anna Paola Maria Luisa Marcello,1 Cristina Vercellati,1 Wilma Barcellini1 1Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 2Department of Oncology and Hemato-Oncology, University of Milan, Milan, ItalyCorrespondence: Bruno Fattizzo, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Hematology Unit, Via F. Sforza 35, Milan, 20122, Italy, Tel +39 0255033477, Email bruno.fattizzo@unimi.itAbstract: Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disease marked by chronic hemolytic anemia of various severity and frequent complications including gallstones, splenomegaly, iron overload, and others. Disease phenotype is highly heterogeneous and changes over time with children, adolescents and adult patients displaying different transfusion requirement and rates of complications. The diagnosis relies on the initial clinical suspicion in a patient with chronic hemolysis and exclusion of other more common congenital forms of hemolytic anemias; it is supported by the demonstration of reduced PK enzyme activity, and further confirmed by the detection of (homozygous or compound heterozygous) mutations of PKLR gene. Therapy is mainly supportive, with vitamin supplementation and transfusions (based on symptoms and patient growth rather than on fixed Hb thresholds). Splenectomy is widely performed, although it is less effective than in membrane defects and carries thrombotic and infectious risk. In the last decade, the allosteric PK enzyme activator mitapivat showed dramatic clinical benefit in clinical trials and gene therapy is also being studied to substitute the defective enzyme. In this review, we provide an insight in the current challenges of PKD diagnosis and management and discuss the future application of novel drugs and gene therapy, including a focus on quality of life.Keywords: pyruvate kinase deficiency, splenectomy, mitapivat, gene therapyhttps://www.dovepress.com/pyruvate-kinase-deficiency-current-challenges-and-future-prospects-peer-reviewed-fulltext-article-JBMpyruvate kinase deficiencysplenectomymitapivatgene therapy. |
| spellingShingle | Fattizzo B Cavallaro F Marcello APML Vercellati C Barcellini W Pyruvate Kinase Deficiency: Current Challenges and Future Prospects Journal of Blood Medicine pyruvate kinase deficiency splenectomy mitapivat gene therapy. |
| title | Pyruvate Kinase Deficiency: Current Challenges and Future Prospects |
| title_full | Pyruvate Kinase Deficiency: Current Challenges and Future Prospects |
| title_fullStr | Pyruvate Kinase Deficiency: Current Challenges and Future Prospects |
| title_full_unstemmed | Pyruvate Kinase Deficiency: Current Challenges and Future Prospects |
| title_short | Pyruvate Kinase Deficiency: Current Challenges and Future Prospects |
| title_sort | pyruvate kinase deficiency current challenges and future prospects |
| topic | pyruvate kinase deficiency splenectomy mitapivat gene therapy. |
| url | https://www.dovepress.com/pyruvate-kinase-deficiency-current-challenges-and-future-prospects-peer-reviewed-fulltext-article-JBM |
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