{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T23:24:02Z","timestamp":1780788242576,"version":"3.54.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that may manifest as neonatal jaundice or acute hemolytic anemia. Quantitative assessment of G6PD activity in erythrocytes is required to definitively diagnose a deficiency. Most males and homozygous females have low enzyme activities, whereas heterozygous females may have a range of activities. We sought to examine G6PD genotype\u2013phenotype associations to identify an activity cutoff above which G6PD deficiency is unlikely.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Ninety-five residual samples were randomly selected to represent the various regions of a G6PD activity distribution. DNA was isolated from the leukocyte fraction and sequenced using the Sanger method. ROC curves were used to establish cutoffs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirteen variant alleles were identified, including 1 not previously reported. In the very deficient activity range, we found males and homozygous females of both class II and III variants. In the deficient category, we found predominantly class III males and heterozygous females. The presumed deficient category contained class III and IV variants and nonvariants. An activity cutoff of &amp;lt;7.85 U\/g hemoglobin (Hb) was 100% sensitive and 94% specific for identifying a G6PD-deficient male, and a cutoff of &amp;lt;8.95 U\/g Hb was 90% sensitive and 82% specific for a deficient female.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The observed activity groupings were not because of a particular variant class. Cutoffs to identify the presence of a deficiency variant for males and females may be useful when trying to decide whether to recommend genetic analysis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1373\/jalm.2017.024935","type":"journal-article","created":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T23:05:21Z","timestamp":1532387121000},"page":"841-850","source":"Crossref","is-referenced-by-count":21,"title":["Genotype\u2013Phenotype Correlations of Glucose-6-Phosphate\u2013Deficient Variants Throughout an Activity Distribution"],"prefix":"10.1093","volume":"2","author":[{"given":"Jennifer L","family":"Powers","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Hunter","family":"Best","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G","family":"Grenache","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,5,1]]},"reference":[{"key":"2022020110204094600_B1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.blre.2007.05.002","article-title":"G6PD deficiency: the genotype-phenotype association","volume":"21","author":"Mason","year":"2007","journal-title":"Blood Rev"},{"key":"2022020110204094600_B2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1182\/blood-2007-04-077412","article-title":"Glucose-6-phosphate dehydrogenase deficiency: a historical perspective","volume":"111","author":"Beutler","year":"2008","journal-title":"Blood"},{"key":"2022020110204094600_B3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0140-6736(08)60073-2","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"371","author":"Cappellini","year":"2008","journal-title":"Lancet"},{"key":"2022020110204094600_B4","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1182\/blood.V84.11.3613.bloodjournal84113613","article-title":"G6PD deficiency","volume":"84","author":"Beutler","year":"1994","journal-title":"Blood"},{"key":"2022020110204094600_B5","first-page":"601","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"67","author":"World Health Organization Working Group","year":"1989","journal-title":"Bull World Health Organ"},{"key":"2022020110204094600_B6","first-page":"243","article-title":"Human glucose-6-phosphate dehydrogenase variants","volume":"45","author":"Yoshida","year":"1971","journal-title":"Bull World Health Organ"},{"key":"2022020110204094600_B7","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.bcmd.2012.01.001","article-title":"Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the \u201cold\u201d and update of the new mutations","volume":"48","author":"Minucci","year":"2012","journal-title":"Blood Cells Mol Dis"},{"key":"2022020110204094600_B8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/iub.137","article-title":"Glucose-6-phosphate dehydrogenase laboratory assay: how, when, and why?","volume":"61","author":"Minucci","year":"2009","journal-title":"IUBMB Life"},{"key":"2022020110204094600_B9","doi-asserted-by":"crossref","first-page":"854","DOI":"10.4269\/ajtmh.14-0194","article-title":"Comparison of quantitative and qualitative tests for glucose-6-phosphate dehydrogenase deficiency","volume":"91","author":"LaRue","year":"2014","journal-title":"Am J Trop Med Hyg"},{"key":"2022020110204094600_B10","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jpeds.2012.04.001","article-title":"Screening for glucose-6-phosphate dehydrogenase deficiency in newborns: practical considerations","volume":"161","author":"Watchko","year":"2012","journal-title":"J Pediatr"},{"key":"2022020110204094600_B11","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1053\/j.semperi.2011.02.010","article-title":"Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: biochemical versus genetic technologies","volume":"35","author":"Kaplan","year":"2011","journal-title":"Semin Perinatol"},{"key":"2022020110204094600_B12","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3109\/00365513.2013.879733","article-title":"Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Greek newborns: the Mediterranean C563T mutation screening","volume":"74","author":"Molou","year":"2014","journal-title":"Scand J Clin Lab Invest"},{"key":"2022020110204094600_B13","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.cca.2013.05.004","article-title":"Determination of optimal cutoff value to accurately identify glucose-6-phosphate dehydrogenase-deficient heterozygous female neonates","volume":"424","author":"Miao","year":"2013","journal-title":"Clin Chim Acta"},{"key":"2022020110204094600_B14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jpeds.2012.02.018","article-title":"Glucose-6-phosphate dehydrogenase deficiency and borderline deficiency: association with neonatal hyperbilirubinemia","volume":"161","author":"Riskin","year":"2012","journal-title":"J Pediatr"},{"key":"2022020110204094600_B15","first-page":"197","article-title":"Quantitative neonatal glucose-6-phosphate dehydrogenase screening: distribution, reference values, and classification by phenotype","volume-title":"J Pediatr","author":"Algur","year":"2012"},{"key":"2022020110204094600_B16","article-title":"Proposal for an Evidence Review Group (ERG) on G6PD testing to support increased access to primaquine for radical cure of Plasmodium vivax and for malaria chemoprophylaxis","volume-title":"Briefing paper for the Malaria Policy Advisory Committee Meeting","author":"Bosman","year":"2013"},{"key":"2022020110204094600_B17","doi-asserted-by":"crossref","first-page":"5906","DOI":"10.1128\/AAC.00600-16","article-title":"Single-dose primaquine in a preclinical model of glucose-6-phosphate dehydrogenase deficiency: implications for use in malaria transmission-blocking programs","volume":"60","author":"Wickham","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"2022020110204094600_B18","unstructured":"National Center for Biotechnology Information. dbSNP: database for short genetic variations. https:\/\/www.ncbi.nlm.nih.gov\/projects\/SNP\/ (Accessed July 2017)."},{"key":"2022020110204094600_B19","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cccn.2004.12.008","article-title":"Glucose-6-phosphate dehydrogenase activity in term and near-term, male African-American neonates","volume":"355","author":"Kaplan","year":"2005","journal-title":"Clin Chim Acta"},{"key":"2022020110204094600_B20","doi-asserted-by":"crossref","first-page":"e0148172","DOI":"10.1371\/journal.pone.0148172","article-title":"Comparison of three screening test kits for G6PD enzyme deficiency: implications for its use in the radical cure of vivax malaria in remote and resource-poor areas in the Philippines","volume":"11","author":"Espino","year":"2016","journal-title":"PLoS One"},{"key":"2022020110204094600_B21","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1006\/bcmd.1997.0147","article-title":"Hematologically important mutations: glucose-6-phosphate dehydrogenase","volume":"23","author":"Vulliamy","year":"1997","journal-title":"Blood Cells Mol Dis"},{"key":"2022020110204094600_B22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/1479-5876-10-199","article-title":"Five novel glucose-6-phosphate dehydrogenase deficiency haplotypes correlating with disease severity","volume":"10","author":"Dallol","year":"2012","journal-title":"J Transl Med"},{"key":"2022020110204094600_B23","doi-asserted-by":"crossref","first-page":"5171","DOI":"10.1073\/pnas.85.14.5171","article-title":"Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia","volume":"85","author":"Vulliamy","year":"1988","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022020110204094600_B24","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/vox.12096","article-title":"Glucose-6-phosphate dehydrogenase deficiency in Italian blood donors: prevalence and molecular defect characterization","volume":"106","author":"Maffi","year":"2014","journal-title":"Vox Sang"},{"key":"2022020110204094600_B25","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1046\/j.1469-1809.1997.6130229.x","article-title":"Genetic heterogeneity of glucose-6-phosphate dehydrogenase deficiency in south-east Sicily","volume":"61","author":"Cittadella","year":"1997","journal-title":"Ann Hum Genet"},{"key":"2022020110204094600_B26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/1475-2875-12-289","article-title":"Evaluation of the phenotypic test and genetic analysis in the detection of glucose-6-phosphate dehydrogenase deficiency","volume":"12","author":"Nantakomol","year":"2013","journal-title":"Malar J"},{"key":"2022020110204094600_B27","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1182\/blood.V74.7.2550.bloodjournal7472550","article-title":"Molecular heterogeneity of glucose-6-phosphate dehydrogenase A","volume":"74","author":"Beutler","year":"1989","journal-title":"Blood"},{"key":"2022020110204094600_B28","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1093\/hmg\/3.5.833","article-title":"The glucose-6-phosphate dehydrogenase (G6PD) deficient variant G6PD Union (454 Arg\u2013&gt;Cys) has a worldwide distribution possibly due to recurrent mutation","volume":"3","author":"Rovira","year":"1994","journal-title":"Hum Mol Genet"},{"key":"2022020110204094600_B29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/humu.9103","article-title":"Glucose-6-phosphate dehydrogenase variants in Malaysian Malays","volume":"21","author":"Ainoon","year":"2002","journal-title":"Hum Mutat"},{"key":"2022020110204094600_B30","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/humu.9367","article-title":"Marked decrease in specific activity contributes to disease phenotype in two human glucose-6-phosphate dehydrogenase mutants. G6PDUnion and G6PDAndalus","volume":"26","author":"Wang","year":"2005","journal-title":"Hum Mutat"}],"container-title":["The Journal of Applied Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/2\/6\/841\/42354640\/2_2_6_841.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/2\/6\/841\/42354640\/2_2_6_841.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T10:21:10Z","timestamp":1643710870000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jalm\/article\/2\/6\/841\/5587535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,1]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,5,1]]},"published-print":{"date-parts":[[2018,5,1]]}},"URL":"https:\/\/doi.org\/10.1373\/jalm.2017.024935","relation":{},"ISSN":["2576-9456","2475-7241"],"issn-type":[{"value":"2576-9456","type":"print"},{"value":"2475-7241","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,5,1]]},"published":{"date-parts":[[2018,5,1]]}}}