Skip to main content
SpringerLink
Log in

Chronic nonspherocytic hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency: report of two families with novel mutations causing G6PD Bangkok and G6PD Bangkok Noi

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common hereditary enzymopathies worldwide. Mostly G6PD deficient cases are asymptomatic though they may have the risk of neonatal jaundice (NNJ) and acute intravascular hemolysis during oxidative stress. Chronic nonspherocytic hemolytic anemia (CNSHA) due to G6PD deficiency is rare. In Thailand, one case was reported 40 years ago and by biochemical study this G6PD was reported to be a new variant G6PD Bangkok. We, herein, report two families with CNSHA due to G6PD deficiency. In the first family, we have been following up the clinical course of the patient with G6PD Bangkok. In addition to chronic hemolysis, he had three acute hemolytic episodes requiring blood transfusions during childhood period. Multiple gallstones were detected at the age of 27. His two daughters who inherited G6PD Bangkok from him and G6PD Vanua Lava from his wife are asymptomatic. Both of them had NNJ and persistent evidences of compensated hemolysis. Molecular analysis revealed a novel missense mutation 825 G→C predicting 275 Lys→Asn causing G6PD Bangkok. In the second family, two male siblings are affected. They had NNJ and several hemolytic episodes which required blood transfusions. On follow-up they have been diagnosed with chronic hemolysis as evidenced by reticulocytosis and indirect hyperbilirubinemia. Molecular analysis revealed combined missense mutations in exons 12 and 13. The first mutation was 1376 G→T predicting 459 Arg→Leu (known as G6PD Canton) and the second one was 1502 T→G predicting 501 Phe→Cys. We designated the resulting novel G6PD variant, G6PD Bangkok Noi.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Luzzatto L, Mehta A, Vulliamy T (2001) Glucose-6-phosphate dehydrogenase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic & molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 4517–4554

    Google Scholar 

  2. Vulliamy T, Luzzatto L, Hirono A, Beutler E (1997) Hematologically important mutations: glucose-6-phosphate dehydrogenase. Blood Cell Mol Dis 23:302–313

    Article  CAS  Google Scholar 

  3. Yoshida A, Beutler E, Motulsky AG (1971) Human glucose-6-phosphate dehydrogenase variants. Bull WHO 45:243–253

    PubMed  CAS  Google Scholar 

  4. Tuchinda S, Rucknagel DL, Na-Nakorn S, Wasi P (1968) Thai variant and the distribution of alleles of 6 phospho-gluconate dehydrogenase and the distribution of glucose-6-phosphate dehydrogenase deficiency in Thailand. Biochem Genet 2:253–264

    Article  PubMed  CAS  Google Scholar 

  5. Panich V (1981) Glucose-6-phosphate dehydrogenase deficiency. Clin Haematol 10:800–814

    PubMed  CAS  Google Scholar 

  6. Tanphaichitr VS, Mahasandana C, Suvatte V, Yodthong S, Pung-amritt P, Seeloem J (1995) Prevalence of hemoglobin E, alpha-thalassemia and glucose-6-phosphate dehydrogenase deficiency in 1, 000 cord bloods studied in Bangkok. Southeast Asian J Trop Med Public Health 26(Suppl 1):271–274

    PubMed  Google Scholar 

  7. Nuchprayoon I, Sanpavat S, Nuchprayoon S (2002) Glucose-6-phosphate dehydrogenase (G6PD) mutations in Thailand: G6PD Viangchan (871G>A) is the most common deficiency variant in the Thai population. Hum Mutat 19:185. doi:10.1002/humu.9010

    Article  PubMed  CAS  Google Scholar 

  8. Talalak P, Beutler E (1969) G-6PD Bangkok: a new variant found in congenital nonspherocytic hemolytic disease (CNSHD). Blood 33:772–776

    PubMed  CAS  Google Scholar 

  9. WHO (1967) Report of WHO Scientific Group, WHO Tech Rep Ser No 366

  10. Beutler E, Blume KG, Kaplan JC et al (1977) International committee for standardization in haematology. recommended methods for red-cell enzyme analysis. Br J Haematol 35:331–340

    Article  PubMed  CAS  Google Scholar 

  11. Hirono A, Miwa S, Fujii H, Ishida F, Yamada K, Kubota K (1994) Molecular study of eight Japanese cases of glucose-6-phosphate dehydrogenase deficiency by non-radioisotopic single-strand conformation polymorphism analysis. Blood 83:3363–3368

    PubMed  CAS  Google Scholar 

  12. Ganczakowski M, Town M, Bowden DK et al (1995) Multiple glucose-6-phosphate dehydrogenase-deficient variants correlate with malaria endemicity in the Vanuatu archipelago (Southwestern Pacific). Am J Hum Genet 56:294–301

    PubMed  CAS  Google Scholar 

  13. Iwai K, Hirono A, Matsuoka H et al (2001) Distribution of glucose-6-phosphate dehydrogenase mutations in Southeast Asia. Hum Genet 108:445–449

    Article  PubMed  CAS  Google Scholar 

  14. Ninokata A, Kimura R, Samakkarn U, Settheetham-Ishida W, Ishida T (2006) Coexistence of five G6PD variants indicates ethnic complexity of Phuket Islanders, Southern Thailand. J Hum Genet 51(5):424–428

    Article  PubMed  Google Scholar 

  15. Stevens DJ, Wanachiwanawin W, Mason PJ, Vulliamy TJ, Luzzatto L (1990) G6PD Canton: a common deficient variant in South East Asia caused by a 459 Arg → Leu mutation. Nucleic Acids Res 18:7190

    Article  PubMed  CAS  Google Scholar 

  16. Huang CS, Hung KL, Huang MJ, Li YC, Liu TH (1996) Neonatal jaundice and molecular mutations in glucose-6-phosphate dehydrogenase deficient newborn infants. Am J Hematol 51:19–25

    Article  PubMed  CAS  Google Scholar 

  17. Shibuya A, Hirono A, Ishii S, Fujii H, Miwa S (1999) Hemolytic crisis after excessive ingestion of fava beans in a male infant with G6PD Canton. Int J Hematol 70:233–235

    PubMed  CAS  Google Scholar 

  18. Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190:372–373

    Article  PubMed  CAS  Google Scholar 

  19. Beutler E, Yeh M, Fairbanks VF (1962) The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD deficiency as a marker. Proc Natl Acad Sci USA 48:9–16

    Article  PubMed  CAS  Google Scholar 

  20. Beutler E (1986) X-inactivation in females heterozygous for G-6-PD variants. In: Yoshida A, Beutler E (eds) Glucose-6-Phosphate dehydrogenase. Academic, New York, pp 405–415

    Google Scholar 

  21. Filosa S, Giacometti N, Wangwei C et al (1996) Somatic-cell selection is a major determinant of the blood-cell phenotype in heterozygotes for glucose-6-phosphate dehydrogenase mutations causing severe enzyme deficiency. Am J Hum Genet 59:887–895

    PubMed  CAS  Google Scholar 

  22. Angsusingh P, Tanphaichitr VS, Suvatte V, Mahasandana C, Tuchinda S (1980) Hyperbilirubinemia in the newborn. Siriraj Hosp Gazette 32:202–214

    Google Scholar 

  23. Tanphaichitr VS (1999) Glucose-6-phosphate dehydrogenase deficiency in Thailand: its significance in the newborn. Southeast Asian J Trop Med Public Health 30(Suppl 2):75–78

    PubMed  Google Scholar 

  24. Mehta A, Mason PJ, Vulliamy TJ (2000) Glucose-6-phosphate dehydrogenase deficiency. Baillières Best Pract Res Clin Haematol 13:21–38

    Article  PubMed  CAS  Google Scholar 

  25. Pongtanakul B, Narkbunnam N, Veerakul G et al (2005) Dengue hemorrhagic fever in patients with thalassemia. J Med Assoc Thai 88(Suppl 8):580–584

    Google Scholar 

  26. Bates GC, Brown CH (1952) Incidence of gallbladder disease in chronic hemolytic anemia (spherocytosis). Gastroenterology 21:104–109

    PubMed  CAS  Google Scholar 

  27. Stephens GC, Scott RB (1980) Cholelithiasis in sickle cell anemia. Arch Intern Med 140:648–651

    Article  PubMed  CAS  Google Scholar 

  28. Chandrcharoensin-Wilde C, Chairoongruang S, Jitnusorn P, Fucharoen S, Vathnopas V (1988) Gallstone in thalassemia. Birth defects Orig Artic Ser 23:263–267

    PubMed  CAS  Google Scholar 

  29. Vathanopas V, Fucharoen S, Chandrcharoensin-Wilde C, Sukrungreung S, Nilakul C (1988) Cholecystectomy in thalassemia. Birth defects Orig Artic Ser 23:269–273

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to the late Dr. Shiro Miwa for his kind encouragement and in debt to Dr. Phumara Talalak for her valuable advice. We also acknowledge the excellent assistance of Miss Darika Seeluam in the preparation of the manuscript.

Author information

Authors and Affiliations

  1. Hematology/Oncology Division, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Pran Nok Road, Bangkok Noi, Bangkok, 10700, Thailand

    Voravarn S. Tanphaichitr, Parichat Pung-amritt & Ajjima Treesucon

  2. Okinaka Memorial Institute for Medical Research, Kishibojin Clinic, Tokyo, Japan

    Akira Hirono

  3. Hematology Division, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Wanchai Wanachiwanawin

Authors
  1. Voravarn S. Tanphaichitr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akira Hirono
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Parichat Pung-amritt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ajjima Treesucon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wanchai Wanachiwanawin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Voravarn S. Tanphaichitr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tanphaichitr, V.S., Hirono, A., Pung-amritt, P. et al. Chronic nonspherocytic hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency: report of two families with novel mutations causing G6PD Bangkok and G6PD Bangkok Noi. Ann Hematol 90, 769–775 (2011). https://doi.org/10.1007/s00277-010-1153-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-010-1153-4

Keywords

Search

Navigation