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Mutation spectrum and enzyme profiling of G6PD deficiency in neonates of north India: a prospective study

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Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked disorder with well-established clinical and allelic heterogeneity and ethnic disparity. With ~390,000 annual births with G6PD deficiency in India, it emerges as the most predictable and preventable inborn metabolic error. Disease prevalence and mutation spectrum have been reasonably reported from central, western and southern parts of India and are mostly retrospective studies. Although prevalence data from north India is available, there is paucity of data on the mutation spectrum and genotype–phenotype correlation (G×P). Thus, we aimed at establishing the clinical and mutation profiles for G6PD, as a part of a large prospective newborn screening study conducted between 2014 and 2016 across hospitals in Delhi, India. G6PD activity levels were measured at 24–48 h of life for ~200,000 neonates using Victor 2D and/or Genomic Screening Processor followed by confirmatory spectrophotometric analysis using RBC lysates of the respective neonates based on clinical symptoms. A subset of 570 enzyme deficient neonates were screened for mutations by polymerase chain reaction-restriction fragment length polymorphism and/or Sanger sequencing. Mediterranean was the most common mutation (n=318; 55.8%) with the lowest enzyme activity and most severe phenotype, followed by G6PD Orissa (n=187;32.8%); Kerala-Kalyan (n=25); Jammu (n=24); Mahidol (n=14); Chattam (n=1) and Nilgiri/Coimbra (n=1). Of the 163 intramural neonates followed up, 68 developed clinical jaundice. However, no correlation was observed between jaundice and enzyme level. Notable outcome of this first ever prospective screening approach for G6PD deficiency in neonates may help in prediction of disease severity and appropriate timely management.

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References

  • Al-Musawi B. M., Al-Allawi N., Abdul-Majeed B. A., Eissa A. A., Jubrael J. M. and Hamamy H. 2012 Molecular characterization of glucose-6-phosphate dehydrogenase deficient variants in Baghdad city: Iraq. BMC Blood Disord. 12, 4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Al-Sweedan S. A. and Awwad N. 2012 Molecular characterization of glucose-6-phosphate dehydrogenase deficiency among Jordanians. Acta Haematol. 128, 195–202.

    Article  CAS  PubMed  Google Scholar 

  • Beutler E. 2008 Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. Blood 111, 16–24.

    Article  CAS  PubMed  Google Scholar 

  • Bhasin M. K. 2006 Genetics of castes and tribes of India: glucose-6-phosphate dehydrogenase deficiency and abnormal haemoglobins (HbS and HbE). Int. J. Hum. Genet. 6, 49–72.

    Article  CAS  Google Scholar 

  • Bizzarro M. J., Colson E. and Ehrenkranz R. A. 2004 Differential diagnosis and management of anemia in the newborn. Pediatr. Clin. North Am. 51, 1087–1107.

    Article  PubMed  Google Scholar 

  • Cappellini M. D., Martinez Di Montemuros F., De Bellis G., Debernardi S., Dotti C. and Fiorelli G. 1996 Multiple G6PD mutations are associated with a clinical and biochemical phenotype similar to that of G6PD Mediterranean. Blood 87, 3953–3958.

    Article  CAS  PubMed  Google Scholar 

  • Çelik H. T., Günbey C., Ünal Ş, Gümrük F. and Yurdakök M. 2013 Glucose-6-phosphate dehydrogenase deficiency in neonatal hyperbilirubinaemia: Hacettepe experbox drawings light down and leftence. J. Paediatr. Child Health 49, 399–402.

    Article  PubMed  Google Scholar 

  • Chalvam R., Kedar P. S., Colah R. B., Ghosh K. and Mukherjee M. B. 2008 A novel R198H mutation in the glucose-6-phosphate dehydrogenase gene in the tribal groups of the Nilgiris in Southern India. J. Hum. Genet. 53, 181–184.

    Article  CAS  PubMed  Google Scholar 

  • de la Caridad Oliva Venereo D. and Viñas Martínez A. L. 2018 Glucose-6-phosphate dehydrogenase deficiency. Rev. Cuba. De Med. Gen. Integral 34, 151–158.

    Google Scholar 

  • Cunningham A. D., Colavin A., Casey K. H. and Mochly-Rosen D. 2017 Coupling between protein stability and catalytic activity determines pathogenicity of G6PD variants. Cell Rep. 18, 2592–2599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devendra R., Gupta V., Shanmugam R., Singh M. P. S. S., Patel P., Valecha N. et al. 2020 Prevalence and spectrum of mutations causing G6PD deficiency in Indian populations. Infect. Genet. Evol. 86, 104597.

    Article  CAS  PubMed  Google Scholar 

  • Devendra R., Shanmugam R., Singh M. P. S. S., Vishwakarma C. P., Godbhole S., Singh N. et al. 2017 Identification of a novel S184F mutation causing glucose-6-phosphate-dehydrogenase deficiency in a tribal family of Madhya Pradesh, Central India. Meta Gene 12, 130–133.

    Article  Google Scholar 

  • Domingo G. J., Advani N., Satyagraha A. W., Sibley C. H., Rowley E., Kalnoky M. et al. 2019 Addressing the gender-knowledge gap in glucose-6-phosphate dehydrogenase deficiency: challenges and opportunities. Int. Health 11, 7–14.

    Article  PubMed  Google Scholar 

  • Davidson R. G., Nitowsky H. M. and Childs B. 1963 Demonstration of two populations of cells in the human female heterozygous for glucose-6-phosphate dehydrogenase variants. Proc. Natl. Acad. Sci. USA 50, 481–485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howes R. E., Piel F. B., Patil A. P., Nyangiri O. A., Gething P. W., Dewi M. et al. 2012 G6PD Deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Med. 9, e1001339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howes R. E., Dewi M., Piel F. B., Monteiro W. M., Battle K. E., Messina J. P. et al. 2013 Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malar J. 12, 418.

    Article  PubMed  PubMed Central  Google Scholar 

  • Joshi S. R., Patel R. Z. and Patel H. R. 2001 High prevalence of G6PD deficiency in Vataliya Prajapati community in western India. Haematologia (budap) 31, 57–60.

    Article  CAS  PubMed  Google Scholar 

  • Kapoor S. and Thelma B. K. 2018 Status of newborn screening and inborn errors of metabolism in India. Indian J. Pediatr. 85, 1110–1117.

    Article  PubMed  Google Scholar 

  • Kumar P., Yadav U. and Rai V. 2016 Prevalence of glucose-6-phosphate dehydrogenase deficiency in India: an updated meta-analysis. Egyptian J. Med. Hum. Genet., https://doi.org/10.1016/j.ejmhg.2016.01.004.

    Article  Google Scholar 

  • Kumar R., Singh M. P. S. S., Mahapatra S., Chaurasia S., Tripathi M. K., Oommen J. et al. 2020 Fine mapping of glucose 6 phosphate dehydrogenase (G6PD) deficiency in a rural malaria area of South West Odisha using the clinical, hematological and molecular approach. Mediterr. J. Hematol. Infect. Dis. 12.

  • Kurdi-Haidar B., Mason P. J., Berrebi A., Ankra-Badu G., Al-Ali A., Oppenheim A. and Luzzatto L. 1990 Origin and spread of the glucose-6-phosphate dehydrogenase variant (G6PD-Mediterranean) in the Middle East. Am. J. Hum. Genet. 47, 1013–1019.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martini G., Toniolo D., Vulliamy T., Luzzatto L., Dono R., Viglietto G. et al. 1986 Structural analysis of the X-linked gene encoding human glucose 6-phosphate dehydrogenase. EMBO J. 5, 1849–1855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minucci A., Moradkhani K., Hwang M. J., Zuppi C., Giardina B. and Capoluongo E. 2012 Glucose-6-phosphate dehydrogenase (G6PD) mutations database: Review of the “old” and update of the new mutations. Blood Cells Mol. Dis. 48, 154–165.

    Article  CAS  PubMed  Google Scholar 

  • Moinuddin M. K., Gagandeep V. and Mutalik S. 2017 Prevalence of glucose 6 phosphate dehydrogenase (G6PD) deficiency in a community by newborn screening. Int. J. Contemp. Pediatr. 4, 1018.

    Article  Google Scholar 

  • Mukherjee M. B., Colah R. B., Martin S. and Ghosh K. 2015 Glucose-6-phosphate dehydrogenase (G6PD) deficiency among tribal populations of India - Country scenario. Indian J. Med. Res. 141, 516.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nair H. 2009 Neonatal screening program for G6PD deficiency in India: need and feasibility. Indian Pediatr. 46, 1045–1049.

    PubMed  Google Scholar 

  • Nkhoma E. T., Poole C., Vannappagari V., Hall S. A. and Beutler E. 2009 The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol. Dis. 42, 267–278.

    Article  CAS  PubMed  Google Scholar 

  • Pietrapertosa A., Palma A., Campanale D., Delios G., Vitucci A. and Tannoia N. 2001 Genotype and phenotype correlation in glucose-6-phosphate dehydrogenase deficiency. Haematologica 86, 30–35.

    CAS  PubMed  Google Scholar 

  • Reddy B. and Tripathy V. 2007 Present status of understanding on the G6PD deficiency and natural selection. J. Postgrad. Med. 53, 193.

    Article  PubMed  Google Scholar 

  • Sukumar S., Mukherjee M. B., Colah R. B. and Mohanty D. 2004 Molecular basis of G6PD deficiency in India. Blood Cells Mol. Dis. 33, 141–145.

    Article  CAS  PubMed  Google Scholar 

  • Tiwari M. 2017 Glucose 6 phosphatase dehydrogenase (G6PD) and neurodegenerative disorders: mapping diagnostic and therapeutic opportunities. Genes Dis. 4, 196–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van den Broek L., Heylen E. and van den Akker M. 2016 Glucose-6-phosphate dehydrogenase deficiency: not exclusively in males. Clin. Case Rep. 4, 1135–1137.

    Article  PubMed  PubMed Central  Google Scholar 

  • Verma J., Roy P., Thomas D. C., Jhingan G., Singh A., Bijarnia-Mahay S. and Verma I. C. 2020 Newborn screening for congenital hypothyroidism, congenital adrenal hyperplasia, and glucose-6-phosphate dehydrogenase deficiency for improving health care in India. J. Pediatr. Intensive Care 9, 40–44.

    Article  PubMed  Google Scholar 

  • WHO Working Group 1989 Glucose-6-phosphate dehydrogenase deficiency. Bull. World Health Organ 67, 601–611.

    Google Scholar 

  • Zahedpasha Y., Ahmadpour Kachouri M., Akhavan Niaki H. and Farhadi R. 2013 Comparison of molecular mutations of G6PD deficiency gene between icteric and nonicteric neonates. Int. J. Mol. Cell Med. 2, 14–20.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Gratefully acknowledge Grant (# IR/SO/LC-0001/2012) to BKT and SK from Science and Engineering Research Board (SERB), New Delhi, India and all the members of SERB-NBS initiative group listed in Annexure; Sanger sequencing and computational facility provided by Central Instrumentation Facility, University of Delhi South Campus (UDSC); infrastructure support provided by the University Grants Commission (UGC), New Delhi, through Special Assistance Programme and Department of Science and Technology, New Delhi, through FIST and DU-DST PURSE (Phase II) programmes to the Department of Genetics, UDSC; Non-NET Fellowship from UGC; and Senior Research Fellowship from Indian Council of Medical Research, New Delhi to UB.

Author information

Authors and Affiliations

  1. Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110 021, India

    Upasana Bhattacharyya, Diksha Sharma, Manpreet Kaur & B. K. Thelma

  2. Division of Genetics and Metabolism, Department of Pediatrics, Lok Nayak Hospital and Maulana Azad Medical College, New Delhi, 110 002, India

    Preeti Deswal, Sunil Kumar Polipalli & Seema Kapoor

Authors
  1. Upasana Bhattacharyya
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  2. Preeti Deswal
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  3. Sunil Kumar Polipalli
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  4. Diksha Sharma
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  5. Manpreet Kaur
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  6. Seema Kapoor
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  7. B. K. Thelma
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Consortia

SERB-NBS Initiative Group

  • Madhulika Kabra
  • , Neerja Gupta
  • , Ramesh Agarwal
  • , A. K. Deorari
  • , V. K. Paul
  • , Shevendru Roy
  • , R. K. Sanjeev
  • , R. S. Tomar
  • , J. S. Bhasin
  • , Amit Tyagi
  • , V. K. Sharma
  • , Anil Gulati
  • , Rajesh Yadav
  • , M. M. A. Faridi
  • , Prerna Batra
  • , Pooja Dewan
  • , Veena Devgan
  • , Alka Mathur
  • , Aseem Bhatnagar
  • , Sunita Bhatia
  • , Ajay Kumar
  • , Sushma Nangia
  • , Arvind Saili
  • , Anju Seth
  • , Deepak Singla
  • , S. K. Arora
  • , S. Mehndiratta
  • , Ashish Jain
  • , Gaurav Pradhan
  • , Sangeeta Gupta
  • , Siddarth Ramji
  • , Mukesh Darshan
  • , S. K. Polipalli
  • , Somesh Kumar
  • , Biju Varughese
  • , Avinash Lomash
  • , Poonam Sidana
  • , Sonia Mitta
  • , Amarjeet Chitkara
  • , Arti Maria
  • , Harish Chellani
  • , K. C. Aggarwa
  • , Shobhna Gupta
  • , Arya Sugandha
  • , Ajay Gambhir
  • , Surinder Bisht
  • , Anand Aggarwal
  • , P. M. Kohli
  •  & Indermeet Singh

Contributions

BKT and SK designed the study and obtained research funding. All clinical collaborators of the SERB-NBS initiative group recruited the neonates; SKP performed confirmatory screening and PD, the clinical follow up of the deficient cohort; UB, DS, MK performed all mutation analysis; UB, PD, SK and BKT wrote the first draft of the manuscript; and all authors contributed and have approved the final manuscript.

Corresponding authors

Correspondence to Seema Kapoor or B. K. Thelma.

Additional information

Corresponding editor: Ashwin Dalal

List of SERB-NBS Initiative Group Members is provided in the Appendix.

Appendix

Appendix

SERB-NBS Initiative Group Members, Delhi: Madhulika Kabra1, Neerja Gupta1, Ramesh Agarwal1, A. K. Deorari1, V. K. Paul1, Shevendru Roy2, R. K. Sanjeev2, R. S. Tomar2, J. S. Bhasin3, Amit Tyagi3, V. K. Sharma4, Anil Gulati4, Rajesh Yadav5, M. M. A. Faridi6, Prerna Batra6, Pooja Dewan6, Veena Devgan7, Alka Mathur7, Aseem Bhatnagar8, Sunita Bhatia9, Ajay Kumar1,10, Sushma Nangia10, Arvind Saili10, Anju Seth10, Deepak Singla11, S. K. Arora12, S. Mehndiratta12, Ashish Jain13, Gaurav Pradhan13, Sangeeta Gupta13, Siddarth Ramji13, Mukesh Darshan13, S. K. Polipalli13, Somesh Kumar13, Biju Varughese13, Avinash Lomash13, Poonam Sidana14, Sonia Mittal,14, Amarjeet Chitkara14, Arti Maria15, Harish Chellani16, K. C. Aggarwal,16, Shobhna Gupta16, Arya Sugandha16, Ajay Gambhir17, Surinder Bisht18, Anand Aggarwal19, P. M. Kohli19, Indermeet Singh19.

Affiliations: 1All India Institute of Medical Sciences, Delhi, India; 2Army and Base Hospital, Delhi, India; 3BLKapoor Hospital, Delhi, India; 4Deen Dayal Hospital, Delhi, India; 5Girdhari Lal Hospital, Delhi, India; 6Guru Teg Bahadur Hospital, Delhi, India; 7Hindu Rao Hospital, Delhi, India; 8Institute of Nuclear Medicine and Allied Sciences, Delhi, India; 9Kasturba Hospital, Delhi, India; 10Lady Hardinge Medical College, Delhi, India; 11Maharaja Agrasen Hospital, Delhi, India; 12Mata Chanan Devi Hospital, Delhi, India; 13Maulana Azad Medical College, Delhi, India; 14Max Super Speciality Hospital, Delhi, India; 15Ram Manohar Lohia Hospital, Delhi, India; 16Safdurjung Hospital and VMM College, Delhi, India; 17Saroj Hospital, Delhi, India; 18Swami Dayanand Hospital, Delhi, India; 19Sanjay Gandhi Hospital, Delhi, India.

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Bhattacharyya, U., Deswal, P., Polipalli, S.K. et al. Mutation spectrum and enzyme profiling of G6PD deficiency in neonates of north India: a prospective study. J Genet 102, 40 (2023). https://doi.org/10.1007/s12041-023-01437-7

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  • DOI: https://doi.org/10.1007/s12041-023-01437-7

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