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Improving the laboratory diagnosis of pyruvate kinase deficiency

Research output: Contribution to journalArticlepeer-review

Claire Laas, Christopher Lambert, Tania Senior McKenzie, Ewart Sheldon, Philip Davidson, David Rees, Barnaby Clark

Original languageEnglish
Pages (from-to)994-1000
Number of pages7
JournalBritish Journal of Haematology
Issue number5
Accepted/In press2021
PublishedJun 2021

Bibliographical note

Funding Information: We thank Julie Kelly who previously worked with Agios Pharmaceuticals for her critical review of the paper. The research study was designed by Barnaby Clark. Claire Laas and Tania Senior McKenzie performed the research and Ewart Sheldon performed statistical analysis. Claire Laas and Barnaby Clark analysed the data and wrote the paper and all the authors reviewed and contributed to the manuscript. Publisher Copyright: © 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


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. in 1977 when the test was first established. The introduction of genetic testing permitted the creation of reference sample datasets, with positive controls having two pathogenic variants causing disease. This permitted re-assessment of the enzyme assay’s sensitivity and specificity, and was used to reassess the reference range of the enzyme assay. Using sequenced samples, we have devised an enzyme assay, DNA testing workflow, which minimises false negative/positive results and improves the diagnostic efficiency. This combined enzyme-DNA testing strategy should improve the diagnostic accuracy whilst limiting the number of expensive DNA tests. During this evaluation, 10 novel genetic variants were identified and are described.

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