Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hemolytic anemia caused by mutations in G6PD gene. The distribution and frequency of genetic variants differ depending on ethnicity and geographical areas. Because of new migrations different variants are now present in Europe. This retrospective study aims to identify variants among the G6PD deficient subjects referred since 2004 to IRCCS Ca’ Granda Foundation Hospital in Milan. The subjects were divided into 3 groups: group 1 (2004–2008), group 2 (2009–2013), and group 3 (2014–2018). During 15 years a significant decrease of the Mediterranean and an important increase of the African, Asian, and uncommon variants (classified as Others) have been observed. Three new mutations were found: in group 2 heterozygosity for c.[1454G > A] (Gly485Asp) in an adult female with severe anemia, high bilirubin levels and G6PD activity of 0,69 (IU/gHb) and heterozygosity for c.[584A > G] (Gln195Arg) in an elderly woman of Italian origin showing only anemia and enzymatic activity of 1,54 (IU/gHb) were detected. In group 3 hemizygosity for c.[670A > T] (Ile224Phe) in an adult Chinese man without anemia but with total absence of G6PD activity was found. These data reflect the appearance of uncommon G6PD mutations in northern Italy, probably due to new migrations, as consequence G6PD characterization becomes a diagnostic issue.
Similar content being viewed by others
References
Nkhoma ET, Poole C, Vannappagari V, Hall SA, Beutler E (2009) The global prevalence of Glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol Dis 42(3):267–278
Luzzatto L, Ally M, Notaro R (2020) Glucose-6-phosphate dehydrogenase deficiency. Blood 136(11):1225–1240
Gomez-Manzo S, Marcial-Quino J, Vanoye-Carlo A, Serrano-Posada H, Ortega-Cuellar D, Gonzales-Valdez A, Castillo-Rodriguez RA, Hernandez-Ochoa B, Sierra-Palacios E, Rodriguez-Bustamante E, Arreguin-Espinosa R (2016) Glucose-6-phosphate dehydrogenase: update and analysis of new mutations around the world. Int Mol Sci 17. https://doi.org/10.3390/ijms17122069
Cappellini MD, Fiorelli G (2008) Glucose-6-phosphate dehydrogenase deficiency. Lancet 371:64–74
Boonyuen U, Chamchoy K, Swangsri T, Junkree T, Day NPJ, White NJ, Imwong M (2017) A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency. Int J Biol Macromol 104:145–156
Ninfali P, Baronciani L, Ruzzo A, Fortini C, Amadori E, Dall’ara G, Magnani M, Beutler E (1993) Molecular analysis of G6PD variants in northern Italy: a study on the population from the Ferrara District. Hum Genet 92:139–142
Fiorelli G, Martinez di Montemuros F, Cappellini MD (2000) Chronic non-spherocytic haemolytic disorders associated with glucose-6-phosphate dehydrogenase variants. Best Pract Res Clin Haematol 13:39–55
Martinez di Montemuros F, Dotti C, Tavazzi D, Fiorelli G, Cappellini MD (1997) Molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) variants in Italy. Haematologica 82:440–445
Luzzatto L (1979) Genetics of red cells and susceptibility to malaria. Blood 54:961–976
Mesba-Namin SA, Sanati MH, Mowjoodi A, Mason PJ, Wuillamy TJ, Noori-Daloii MR (2002) Threee major glucose-6-phosphate dhydrogenase-deficient polymorphic variants identified in Mazandaran satet of Iran. Brit J Hematol 117:763–764
Sirdah MM, Shubair ME, Al-Khalout MS, Al-Tayeb JM, Prchal JT, Scott Reading N (2017) Possible association of 3′ UTR +357 a>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency. Hematology 22:370–374
Moiz B, Nasir A, Moatter T, Naqvi ZA, Khurshid M (2009) Population study of 1311 C/T polymorphism of glucose 6 phosphate dehydrogenase gene in Pakistan—an analysis of 715 X chromosomes. BMC Genet 10. https://doi.org/10.1186/1471-2156-10-41
Luzzato L, Nannelli C, Notaro R (2016) Glucose-6-phosphate dehydrogenase deficiency. Hematol Oncol Clin North Am 30(2):373–393
Jiang W, Yu G, Liu P, Geng Q, Chen L, Lin Q, Ren X, Ye W, He Y, Guo Y, Duan S, Wen J, Li H, Qi Y, Jiang C, Zheng Y, Liu C, Si E, Zhang Q et al (2006) Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in Chinese population. Hum Genet 119(5):463–478
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethics approval
All procedures performed in this study involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Consent to participate
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Duca, L., Nava, I., Tavazzi, D. et al. Epidemiological shift of glucose-6-phosphate dehydrogenase mutations in northern Italy in the last 15 years. Ann Hematol 100, 2683–2688 (2021). https://doi.org/10.1007/s00277-021-04630-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-021-04630-9