{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:51:27Z","timestamp":1789163487907,"version":"build-2803163510"},"reference-count":102,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a prevalent condition worldwide and is caused by loss-of-function mutations in the G6PD gene. Individuals with deficiency are more susceptible to oxidative stress which leads to the classical, acute hemolytic anemia (favism). However, G6PD deficiency in newborn infants presents with an increased risk of hyperbilirubinemia, that may rapidly escalate to result in bilirubin induced neurologic dysfunction (BIND). Often with no overt signs of hemolysis, G6PD deficiency in the neonatal period appears to be different in the pathophysiology from favism. This review discusses and compares the mechanistic pathways involved in these two clinical presentations of this enzyme disorder. In contrast to the membrane disruption of red blood cells and Heinz bodies formation in favism, G6PD deficiency causing jaundice is perhaps attributed to the disruption of oxidant-antioxidant balance, impaired recycling of peroxiredoxin 2, thus affecting bilirubin clearance. Screening for G6PD deficiency and close monitoring of affected infants are important aspects in neonatal care to prevent kernicterus, a permanent and devastating neurological damage. WHO recommends screening for G6PD activity of all infants in countries with high prevalence of this deficiency. The traditional fluorescent spot test as a screening tool, although low in cost, misses a significant proportion of cases with moderate deficiency or the partially deficient, heterozygote females. Some newer and emerging laboratory tests and diagnostic methods will be discussed while developments in genomics and proteomics contribute to increasing studies that spatially profile genetic mutations within the protein structure that could predict their functional and structural effects. In this review, several known variants of G6PD are highlighted based on the location of the mutation and amino acid replacement. These could provide insights on why some variants may cause a higher degree of phenotypic severity compared to others. Further studies are needed to elucidate the predisposition of some variants toward certain clinical manifestations, particularly neonatal hyperbilirubinemia, and how some variants increase in severity when co-inherited with other blood- or bilirubin-related genetic disorders.<\/jats:p>","DOI":"10.3389\/fped.2022.875877","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T01:22:55Z","timestamp":1653355375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":82,"title":["Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity"],"prefix":"10.3389","volume":"10","author":[{"given":"Heng Yang","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azlin","family":"Ithnin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja Zahratul","family":"Azma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainoon","family":"Othman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armindo","family":"Salvador","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fook Choe","family":"Cheah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1046\/j.1432-1327.1998.2510382.x","article-title":"Amino acid substitutions at the dimer interface of human glucose-6-phosphate dehydrogenase that increase thermostability and reduce the stabilising effect of NADP.","volume":"251","author":"Scopes","year":"1998","journal-title":"Eur J Biochem."},{"key":"B2","doi-asserted-by":"publisher","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":"B3","doi-asserted-by":"publisher","first-page":"21179","DOI":"10.3390\/ijms151121179","article-title":"The stability of G6PD is affected by mutations with different clinical phenotypes.","volume":"15","author":"G\u00f3mez-Manzo","year":"2014","journal-title":"Int J Mol Sci."},{"key":"B4","first-page":"405","article-title":"Semiquantitative screening test for G6PD deficiency detects severe deficiency but misses a substantial proportion of partially-deficient females.","volume":"34","author":"Ainoon","year":"2003","journal-title":"Southeast Asian J Trop Med Public Health."},{"key":"B5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3109\/08880018.2013.871613","article-title":"Why does the Iranian national program of screening newborns for G6PD enzyme deficiency miss a large number of affected infants?","volume":"31","author":"Kosaryan","year":"2014","journal-title":"Pediatr Hematol Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.bcmd.2008.12.005","article-title":"The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis.","volume":"42","author":"Nkhoma","year":"2009","journal-title":"Blood Cells Mol Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e1001339","DOI":"10.1371\/journal.pmed.1001339","article-title":"G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map.","volume":"9","author":"Howes","year":"2012","journal-title":"PLoS Med."},{"key":"B8","first-page":"601","article-title":"Glucose-6-phosphate dehydrogenase deficiency.","volume":"67","year":"1989","journal-title":"Bull World Health Organ."},{"key":"B9","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/pr.2013.208","article-title":"Neonatal hyperbilirubinemia and rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels.","volume":"74","author":"Bhutani","year":"2013","journal-title":"Pediatr Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0179550","DOI":"10.1371\/journal.pone.0179550","article-title":"Report about term infants with severe hyperbilirubinemia undergoing exchange transfusion in Southwestern China during an 11-year period, from 2001 to 2011.","volume":"12","author":"Yu","year":"2017","journal-title":"PLoS One."},{"key":"B11","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1159\/000445708","article-title":"Neonatal jaundice in low- and middle-income countries: lessons and future directions from the 2015 Don Ostrow Trieste Yellow Retreat.","volume":"110","author":"Greco","year":"2016","journal-title":"Neonatology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1159\/000207822","article-title":"Red cell metabolism and severe neonatal jaundice in West Malaysia.","volume":"58","author":"Lie-Injo","year":"1977","journal-title":"Acta Haematol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1136\/bmj.292.6517.397","article-title":"Glucose-6-phosphate dehydrogenase deficiency: a preventable cause of mental retardation.","volume":"292","author":"Singh","year":"1986","journal-title":"Br Med J (Clin Res Ed)."},{"key":"B14","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1111\/jpc.13509","article-title":"Glucose-6-phosphate dehydrogenase (G6PD)-deficient infants: enzyme activity and gene variants as risk factors for phototherapy in the first week of life.","volume":"53","author":"Wong","year":"2017","journal-title":"J Paediatr Child Health."},{"key":"B15","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1159\/000489820","article-title":"Hemolysis and glucose-6-phosphate dehydrogenase deficiency-related neonatal hyperbilirubinemia.","volume":"114","author":"Kaplan","year":"2018","journal-title":"Neonatology."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5209","DOI":"10.1002\/j.1460-2075.1995.tb00205.x","article-title":"Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress.","volume":"14","author":"Pandolfi","year":"1995","journal-title":"EMBO J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1089\/ars.2008.2081","article-title":"Peroxiredoxin 2 and peroxide metabolism in the erythrocyte.","volume":"10","author":"Low","year":"2008","journal-title":"Antioxid Redox Signal."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mam.2008.08.006","article-title":"Glutathione: overview of its protective roles, measurement, and biosynthesis.","volume":"30","author":"Forman","year":"2009","journal-title":"Mol Aspects Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1056\/nejmra1708111","article-title":"Favism and glucose-6-phosphate dehydrogenase deficiency.","volume":"378","author":"Luzzatto","year":"2018","journal-title":"N Engl J Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1096\/fj.14-250050","article-title":"Increased basal oxidation of peroxiredoxin 2 and limited peroxiredoxin recycling in glucose-6-phosphate dehydrogenase-deficient erythrocytes from newborn infants.","volume":"28","author":"Cheah","year":"2014","journal-title":"FASEB J."},{"key":"B21","first-page":"137","article-title":"The genetics of glucose-6-phosphate dehydrogenase deficiency.","volume":"27","author":"Beutler","year":"1990","journal-title":"Semin Hematol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e13031","DOI":"10.1371\/journal.pone.0013031","article-title":"Relating mutant genotype to phenotype via quantitative behavior of the NADPH redox cycle in human erythrocytes.","volume":"5","author":"Coelho","year":"2010","journal-title":"PLoS One."},{"key":"B23","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1046\/j.1365-2141.2001.02526.x","article-title":"Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain: clinical and molecular studies.","volume":"112","author":"Corrons","year":"2001","journal-title":"Br J Haematol."},{"key":"B24","doi-asserted-by":"publisher","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":"B25","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.3390\/ijms17122069","article-title":"Glucose-6-phosphate dehydrogenase: update and analysis of new mutations around the world.","volume":"17","author":"G\u00f3mez-Manzo","year":"2016","journal-title":"Int J Mol Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1159\/000510300","article-title":"A novel variant in G6PD (c.1375C>G) identified from a hispanic neonate with extreme hyperbilirubinemia and low G6PD enzymatic activity.","volume":"117","author":"Bahr","year":"2020","journal-title":"Neonatology."},{"key":"B27","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12881-020-01090-2","article-title":"A novel G6PD deleterious variant identified in three families with severe glucose-6-phosphate dehydrogenase deficiency.","volume":"21","author":"Tong","year":"2020","journal-title":"BMC Med Genet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/s10038-019-0700-7","article-title":"Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flow-through hybridisation. J Hum Genet. 65(3), 263-270.","volume":"65","author":"Alina","year":"2020","journal-title":"Erratum in J Hum Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s40246-021-00358-9","article-title":"Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population.","volume":"15","author":"Malik","year":"2021","journal-title":"Hum Genomics."},{"key":"B30","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1182\/blood.V85.1.257.bloodjournal851257","article-title":"Glucose-6 phosphate dehydrogenase mutations and haplotypes in various ethnic groups.","volume":"85","author":"Xu","year":"1995","journal-title":"Blood"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e2545","DOI":"10.1038\/cddis.2016.463","article-title":"Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.","volume":"8","author":"Chen","year":"2017","journal-title":"Cell Death Dis."},{"key":"B32","first-page":"243","article-title":"Human glucose-6-phosphate dehydrogenase variants.","volume":"45","author":"Yoshida","year":"1971","journal-title":"Bull World Health Organ."},{"key":"B33","doi-asserted-by":"publisher","first-page":"17106","DOI":"10.1038\/s41598-020-74200-y","article-title":"Glucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype-phenotype association throughout an activity distribution.","volume":"10","author":"He","year":"2020","journal-title":"Sci Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.ymgme.2016.03.008","article-title":"Detailed functional analysis of two clinical glucose-6-phosphate dehydrogenase (G6PD) variants, G6PDViangchan and G6PDViangchan+Mahidol: decreased stability and catalytic efficiency contribute to the clinical phenotype.","volume":"118","author":"Boonyuen","year":"2016","journal-title":"Mol Genet Metab."},{"key":"B35","first-page":"30","article-title":"Genotype and phenotype correlation in glucose-6-phosphate dehydrogenase deficiency.","volume":"86","author":"Pietrapertosa","year":"2001","journal-title":"Haematologica."},{"key":"B36","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/j.1651-2227.1994.tb13216.x","article-title":"Severe neonatal jaundice associated with glucose-6-phosphate dehydrogenase deficiency: pathogenesis and global epidemiology.","volume":"394","author":"Valaes","year":"1994","journal-title":"Acta Paediatr Suppl."},{"key":"B37","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/s0095-5108(18)30098-8","article-title":"Severe neonatal hyperbilirubinemia. A potential complication of glucose-6-phosphate dehydrogenase deficiency.","volume":"25","author":"Kaplan","year":"1998","journal-title":"Clin Perinatol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.bcmd.2016.07.001","article-title":"Favism, the commonest form of severe hemolytic anemia in Palestinian children, varies in severity with three different variants of G6PD deficiency within the same community.","volume":"60","author":"Reading","year":"2016","journal-title":"Blood Cells Mol Dis."},{"key":"B39","doi-asserted-by":"publisher","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 USA."},{"key":"B40","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.bcmd.2012.06.003","article-title":"Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Gaza Strip Palestinians.","volume":"49","author":"Sirdah","year":"2012","journal-title":"Blood Cells Mol Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/S0022-3476(75)80148-X","article-title":"Hydrops fetalis associated with erythrocyte G-6-PD deficiency and maternal ingestion of fava beans and ascorbic acid.","volume":"86","author":"Mentzer","year":"1975","journal-title":"J Pediatr."},{"key":"B42","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/s0022-3476(95)70178-8","article-title":"Favism in a female newborn infant whose mother ingested fava beans before delivery.","volume":"127","author":"Corchia","year":"1995","journal-title":"J Pediatr."},{"key":"B43","first-page":"477","article-title":"Favism by proxy in nursing glucose-6-phosphate dehydrogenase-deficient neonates.","volume":"18","author":"Kaplan","year":"1998","journal-title":"J Perinatol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1136\/adc.46.245.121","article-title":"Favism in breast-fed infants.","volume":"46","author":"Taj-Eldin","year":"1971","journal-title":"Arch Dis Child."},{"key":"B45","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1111\/j.1553-2712.2000.tb01889.x","article-title":"Association of naphthalene with acute hemolytic anemia.","volume":"7","author":"Santucci","year":"2000","journal-title":"Acad Emerg Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e3147","DOI":"10.7759\/cureus.3147","article-title":"Naphthalene toxicity: methemoglobinemia and acute intravascular hemolysis.","volume":"10","author":"Volney","year":"2018","journal-title":"Cureus."},{"key":"B47","first-page":"740","article-title":"Severe haemolytic anaemia due to ingestion of naphthalene (mothball) containing coconut oil.","volume":"22","author":"Rahman","year":"2012","journal-title":"J Coll Physicians Surg Pak."},{"key":"B48","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/1752-1947-2-146","article-title":"Kernicterus by glucose-6-phosphate dehydrogenase deficiency: a case report and review of the literature.","volume":"2","author":"de Gurrola","year":"2008","journal-title":"J Med Case Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"150","DOI":"10.5694\/j.1326-5377.2011.tb04203.x","article-title":"Risk of brain damage in babies from naphthalene in mothballs: call to consider a national ban.","volume":"194","author":"Tarnow-Mordi","year":"2011","journal-title":"Med J Aust."},{"key":"B50","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/ijlh.13713","article-title":"Henna-induced Heinz bodies in glucose-6-phosphate dehydrogenase-deficient newborn.","volume":"44","author":"Khefacha","year":"2022","journal-title":"Int J Lab Hematol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1016\/s0022-3476(63)80221-8","article-title":"Acute haemolysis due to naphthalene inhalation.","volume":"63","author":"Valaes","year":"1963","journal-title":"J Pediatr."},{"key":"B52","doi-asserted-by":"publisher","first-page":"F534","DOI":"10.1136\/fn.88.6.F534","article-title":"Massive acute haemolysis in neonates with glucose-6-phosphate dehydrogenase deficiency.","volume":"88","author":"Dhillon","year":"2003","journal-title":"Arch Dis Child Fetal Neonatal Ed."},{"key":"B53","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1126\/science.124.3220.484-a","article-title":"Enzymatic deficiency in primaquine-sensitive erythrocytes.","volume":"124","author":"Carson","year":"1956","journal-title":"Science."},{"key":"B54","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/s0268-960x(96)90019-3","article-title":"G6PD: population genetics and clinical manifestations.","volume":"10","author":"Beutler","year":"1996","journal-title":"Blood Rev."},{"key":"B55","doi-asserted-by":"publisher","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":"B56","doi-asserted-by":"publisher","first-page":"722","DOI":"10.7326\/0003-4819-74-5-722","article-title":"Chloramphenicol-induced hemolysis in Caucasian glucose-6-phosphate dehydrogenase deficiency.","volume":"74","author":"McCaffrey","year":"1971","journal-title":"Ann Intern Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/BF02756215","article-title":"Acute haemolytic anaemia in typhoid fever.","volume":"39","author":"Bakshi","year":"1972","journal-title":"Indian J Pediatr."},{"key":"B58","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/s0140-6736(73)91602-4","article-title":"Glucose-6-phosphate-dehydrogenase deficiency in Nigerians with jaundice associated with lobar pneumonia.","volume":"1","author":"Tugwell","year":"1973","journal-title":"Lancet."},{"key":"B59","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1093\/milmed\/163.6.434","article-title":"Hepatitis A and cytomegalovirus infection precipitating acute hemolysis in glucose-6-phosphate dehydrogenase deficiency.","volume":"163","author":"Siddiqui","year":"1998","journal-title":"Mil Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1155\/2003\/913679","article-title":"Case report: acute hepatitis E infection with coexistent glucose-6-phosphate dehydrogenase deficiency.","volume":"14","author":"Monga","year":"2003","journal-title":"Can J Infect Dis."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1172\/JCI106747","article-title":"Oxidant injury of caucasian glucose-6-phosphate dehydrogenase-deficient red blood cells by phagocytosing leukocytes during infection.","volume":"50","author":"Baehner","year":"1971","journal-title":"J Clin Invest."},{"key":"B62","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1111\/j.1651-2227.1976.tb18006.x","article-title":"Erythrocyte glucose 6-phosphate dehydrogenase deficiency (G6PD type A-) and neonatal jaundice.","volume":"65","author":"Bienzle","year":"1976","journal-title":"Acta Paediatr Scand."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1111\/apa.12735","article-title":"Addressing the burden of neonatal hyperbilirubinaemia in countries with significant glucose-6-phosphate dehydrogenase deficiency.","volume":"103","author":"Olusanya","year":"2014","journal-title":"Acta Paediatr."},{"key":"B64","doi-asserted-by":"publisher","first-page":"106","DOI":"10.3345\/kjp.2017.60.4.106","article-title":"Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency.","volume":"60","author":"Isa","year":"2017","journal-title":"Korean J Pediatr."},{"key":"B65","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1542\/pir.27-12-443","article-title":"Neonatal jaundice.","volume":"27","author":"Maisels","year":"2006","journal-title":"Pediatr Rev."},{"key":"B66","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/S0022-3476(67)80410-4","article-title":"Life-span of the fetal red blood cell.","volume":"70","author":"Pearson","year":"1967","journal-title":"J Pediatr."},{"key":"B67","first-page":"45","article-title":"The erythrocyte differential count in newborn infants.","volume":"5","author":"Zipursky","year":"1983","journal-title":"Am J Pediatr Hematol Oncol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1073\/pnas.75.3.1213","article-title":"Ligandin retains and albumin loses bilirubin binding capacity in liver cytosol.","volume":"75","author":"Listowsky","year":"1978","journal-title":"Proc Natl Acad Sci USA."},{"key":"B69","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1053\/gast.2002.34173","article-title":"Glucose-6-phosphate dehydrogenase deficiency, the UDP-glucuronosyl transferase 1A1 gene, and neonatal hyperbilirubinemia.","volume":"123","author":"Huang","year":"2002","journal-title":"Gastroenterology."},{"key":"B70","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1182\/blood.v31.3.388.388","article-title":"The catabolism of Heinz bodies: an experimental model demonstrating conversion to non-bilirubin catabolites.","volume":"31","author":"Goldstein","year":"1968","journal-title":"Blood."},{"key":"B71","first-page":"982","article-title":"G6PD enzyme activity in normal term Malaysian neonates and adults using a OSMMR2000-D kit with Hb normalization.","volume":"41","author":"Azma","year":"2010","journal-title":"Southeast Asian J Trop Med Public Health."},{"key":"B72","doi-asserted-by":"publisher","first-page":"e0196716","DOI":"10.1371\/journal.pone.0196716","article-title":"Validation of the quantitative point-of-care CareStart biosensor for assessment of G6PD activity in venous blood.","volume":"13","author":"Bancone","year":"2018","journal-title":"PLoS One."},{"key":"B73","doi-asserted-by":"publisher","first-page":"e0226927","DOI":"10.1371\/journal.pone.0226927","article-title":"Evaluation of quantitative biosensor for glucose-6-phosphate dehydrogenase activity detection.","volume":"14","author":"Pengboon","year":"2019","journal-title":"PLoS One."},{"key":"B74","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1093\/tropej\/fmaa003","article-title":"Evaluation of the diagnostic accuracy of the CareStart\u2122 glucose-6-phosphate dehydrogenase deficiency rapid diagnostic test among Chinese newborns.","volume":"66","author":"Yu","year":"2020","journal-title":"J Trop Pediatr."},{"key":"B75","doi-asserted-by":"publisher","first-page":"e1268","DOI":"10.1542\/peds.2015-2122","article-title":"Point-of-care quantitative measure of glucose-6-phosphate dehydrogenase enzyme deficiency.","volume":"136","author":"Bhutani","year":"2015","journal-title":"Pediatrics."},{"key":"B76","first-page":"15013","article-title":"Molecular epidemiological investigation of G6PD deficiency by a gene chip among Chinese Hakka of southern Jiangxi province.","volume":"8","author":"Hu","year":"2015","journal-title":"Int J Clin Exp Pathol."},{"key":"B77","first-page":"89","article-title":"Complete molecular characterisation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a group of Malaysian Chinese neonates.","volume":"26","author":"Ainoon","year":"2004","journal-title":"Malays J Pathol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1111\/j.1445-5994.2011.02456.x","article-title":"Prevalence and molecular study of G6PD deficiency in Malaysian Orang Asli.","volume":"41","author":"Amini","year":"2011","journal-title":"Intern Med J."},{"key":"B79","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1006\/bcmd.1995.0010","article-title":"Three new exon 10 glucose-6-phosphate dehydrogenase mutations.","volume":"21","author":"Beutler","year":"1995","journal-title":"Blood Cells Mol Dis."},{"key":"B80","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/s1079-9796(03)00119-0","article-title":"Glucose-6-phosphate dehydrogenase (G-6-PD) mutations in Mexico: four new G-6-PD variants.","volume":"31","author":"Vaca","year":"2003","journal-title":"Blood Cells Mol Dis."},{"key":"B81","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1002\/pbc.21715","article-title":"A novel G6PD mutation leading to chronic hemolytic anemia.","volume":"51","author":"McDade","year":"2008","journal-title":"Pediatr Blood Cancer."},{"key":"B82","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1053\/beha.1999.0055","article-title":"Glucose-6-phosphate dehydrogenase deficiency.","volume":"13","author":"Mehta","year":"2000","journal-title":"Baillieres Best Pract Res Clin Haematol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/s0969-2126(00)00104-0","article-title":"Human glucose-6-phosphate dehydrogenase: the crystal structure reveals a structural NADP+ molecule and provides insights into enzyme deficiency.","volume":"8","author":"Au","year":"2000","journal-title":"Structure."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1110\/ps.035352.108","article-title":"What is the role of the second \u201cstructural\u201d NADP+-binding site in human glucose 6-phosphate dehydrogenase?","volume":"17","author":"Wang","year":"2008","journal-title":"Protein Sci."},{"key":"B85","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1056\/NEJM199101173240306","article-title":"Glucose-6-phosphate dehydrogenase deficiency.","volume":"324","author":"Beutler","year":"1991","journal-title":"N Engl J Med."},{"key":"B86","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/j.1432-1033.1969.tb00488.x","article-title":"Subunit interactions of glucose-6-phosphate dehydrogenase from human erythrocytes.","volume":"8","author":"Cohen","year":"1969","journal-title":"Eur J Biochem."},{"key":"B87","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/j.1365-2141.2009.08044.x","article-title":"Glucose 6-phosphate dehydrogenase Palermo R257M: a novel variant associated with chronic non-spherocytic haemolytic anaemia.","volume":"149","author":"Rigano","year":"2010","journal-title":"Br J Haematol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"787","DOI":"10.3390\/ijms17050787","article-title":"Functional and biochemical characterization of three recombinant human glucose-6-phosphate dehydrogenase mutants: Zacatecas, Vanua-Lava and Viangchan.","volume":"17","author":"G\u00f3mez-Manzo","year":"2016","journal-title":"Int J Mol Sci."},{"key":"B89","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/0022-5193(66)90112-3","article-title":"Relations between chemical structure and biological activity in peptides.","volume":"12","author":"Sneath","year":"1966","journal-title":"J Theor Biol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1126\/science.185.4154.862","article-title":"Amino acid difference formula to help explain protein evolution.","volume":"185","author":"Grantham","year":"1974","journal-title":"Science."},{"key":"B91","doi-asserted-by":"crossref","first-page":"5868","DOI":"10.1093\/nar\/17.14.5868","article-title":"G6PD mahidol, a common deficient variant in South East Asia is caused by a (163)glycine\u2014-serine mutation.","volume":"17","author":"Vulliamy","year":"1989","journal-title":"Nucleic Acids Res."},{"key":"B92","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.ymgme.2007.08.122","article-title":"Purification and detailed study of two clinically different human glucose 6-phosphate dehydrogenase variants, G6PD(Plymouth) and G6PD(Mahidol): evidence for defective protein folding as the basis of disease.","volume":"93","author":"Huang","year":"2008","journal-title":"Mol Genet Metab."},{"key":"B93","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1182\/blood.v81.8.2150.bloodjournal8182150","article-title":"Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in patients of Chinese descent and identification of new base substitutions in the human G6PD gene.","volume":"81","author":"Chiu","year":"1993","journal-title":"Blood."},{"key":"B94","doi-asserted-by":"publisher","first-page":"e2022790118","DOI":"10.1073\/pnas.2022790118","article-title":"Long-range structural defects by pathogenic mutations in most severe glucose-6-phosphate dehydrogenase deficiency.","volume":"118","author":"Horikoshi","year":"2021","journal-title":"Proc Natl Acad Sci USA."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1182\/blood.2019000944","article-title":"Glucose-6-phosphate dehydrogenase deficiency.","volume":"136","author":"Luzzatto","year":"2020","journal-title":"Blood."},{"key":"B96","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13023-021-01693-9","article-title":"Genetic spectrum and clinical early natural history of glucose-6-phosphate dehydrogenase deficiency in Mexican children detected through newborn screening.","volume":"16","author":"Vela-Amieva","year":"2021","journal-title":"Orphanet J Rare Dis."},{"key":"B97","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1309\/LMQOSC1RY6ECTDU2","article-title":"G6PD Deficiency and G6PD (Mediterranean and Silent) polymorphisms in Egyptian infants with neonatal hyperbilirubinemia.","volume":"44","author":"Ezz El-Deen","year":"2013","journal-title":"Lab Med."},{"key":"B98","doi-asserted-by":"publisher","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":"B99","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/1471-2431-12-126","article-title":"Neonatal hyperbilirubinemia in infants with G6PD c.563C > T Variant. BMC Pediatr. 12, 126.","volume":"16","author":"Moiz","year":"2012","journal-title":"Erratum in BMC Pediatr."},{"key":"B100","doi-asserted-by":"publisher","first-page":"e27","DOI":"10.1111\/ijlh.12455","article-title":"Severe neonatal jaundice due to a de novo glucose-6-phosphate dehydrogenase deficient mutation.","volume":"38","author":"Del Orbe Barreto","year":"2016","journal-title":"Int J Lab Hematol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"e497","DOI":"10.1097\/MPH.0000000000000435","article-title":"Severe G6PD deficiency due to a new missense mutation in an infant of Northern European descent.","volume":"37","author":"Warny","year":"2015","journal-title":"J Pediatr Hematol Oncol."},{"key":"B102","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.freeradbiomed.2014.10.009","article-title":"A primer on peroxiredoxin biochemistry.","volume":"80","author":"Karplus","year":"2015","journal-title":"Free Radic Biol Med."}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.875877\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T01:23:09Z","timestamp":1653355389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.875877\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,24]]},"references-count":102,"alternative-id":["10.3389\/fped.2022.875877"],"URL":"https:\/\/doi.org\/10.3389\/fped.2022.875877","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,24]]},"article-number":"875877"}}