Seminars in Fetal & Neonatal Medicine
Volume 15, Issue 3 , Pages 148-156 , June 2010

Glucose-6-phosphate dehydrogenase deficiency and severe neonatal hyperbilirubinemia: a complexity of interactions between genes and environment

  • Michael Kaplan

      Affiliations

    • Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
    • Faculty of Medicine of the Hebrew University, Jerusalem, Israel
    • Corresponding Author InformationCorresponding author. Department of Neonatology, Shaare Zedek Medical Center, PO Box 3235, Jerusalem 91031, Israel. Tel.: +972 2 655 5643; fax: +972 2 655 5998.
  • ,
  • Cathy Hammerman

      Affiliations

    • Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
    • Faculty of Medicine of the Hebrew University, Jerusalem, Israel

References 

  1. Nkhoma ET, Poole C, Vannappagari V, Hall SA, Beutler E. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol Dis. 2009;42:267–278
  2. Beutler E. G6PD deficiency. Blood. 1994;84:3613–3636
  3. Luzzatto L. Glucose 6-phosphate dehydrogenase deficiency: from genotype to phenotype. Haematologica. 2006;91:1303–1306
  4. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371:64–74
  5. Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM. Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). J Perinatol. 2009;29(Suppl. 1):S25–S45
  6. Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. Can Med Assoc J. 2006;175:587–590
  7. AlOtaibi SF, Blaser S, MacGregor DL. Neurological complications of kernicterus. Can J Neurol Sci. 2005;32:311–315
  8. Manning D, Todd P, Maxwell M, Jane Platt M. Prospective surveillance study of severe hyperbilirubinaemia in the newborn in the UK and Ireland. Arch Dis Child Fetal Neonatal Ed. 2007;92:F342–F346
  9. Kaplan M, Hammerman C. Severe neonatal hyperbilirubinemia. A potential complication of glucose-6-phosphate dehydrogenase deficiency. Clin Perinatol. 1998;25:575–590
  10. Kaplan M, Hammerman C. Glucose-6-phosphate dehydrogenase deficiency: a potential source of severe neonatal hyperbilirubinaemia and kernicterus. Semin Neonatol. 2002;7:121–128
  11. Kaplan M, Hammerman C. Glucose-6-phosphate dehydrogenase deficiency: a hidden risk for kernicterus. Semin Perinatol. 2004;28:356–364
  12. Valaes T. Severe neonatal jaundice associated with glucose-6-phosphate dehydrogenase deficiency: pathogenesis and global epidemiology. Acta Paediatr Suppl. 1994;394:58–76
  13. Kaplan M, Muraca M, Vreman HJ, et al. Neonatal bilirubin production–conjugation imbalance: effect of glucose-6-phosphate dehydrogenase deficiency and borderline prematurity. Arch Dis Child Fetal Neonatal Ed. 2005;90:F123–F127
  14. Ahlfors CE, Wennberg RP, Ostrow JD, Tiribelli C. Unbound (free) bilirubin: improving the paradigm for evaluating neonatal jaundice. Clin Chem. 2009;55:1288–1299
  15. Watchko JF. Identification of neonates at risk for hazardous hyperbilirubinemia: emerging clinical insights. Pediatr Clin North Am. 2009;56:671–687
  16. Bhutani VK, Johnson L. Kernicterus in the 21st century: frequently asked questions. J Perinatol. 2009;29(Suppl. 1):S20–S24
  17. Zangen S, Kidron D, Gelbart T, Roy-Chowdhury N, Wang X, Kaplan M. Fatal kernicterus in a girl deficient in glucose-6-phosphate dehydrogenase: a paradigm of synergistic heterozygosity. J Pediatr. 2009;154:616–619
  18. Kaplan M, Renbaum P, Levy-Lahad E, Hammerman C, Lahad A, Beutler E. Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci USA. 1997;94:12128–12132
  19. Huang CS, Chang PF, Huang MJ, Chen ES, Chen WC. Glucose-6-phosphate dehydrogenase deficiency, the UDP-glucuronosyl transferase 1A1 gene, and neonatal hyperbilirubinemia. Gastroenterology. 2002;123:127–133
  20. Subcommittee on Hyperbilirubinemia , American Academy of Pediatrics . Clinical practice guideline: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114:297–316
  21. Kaplan M, Hammerman C, Vreman HJ, Wong RJ, Stevenson DK. Severe hemolysis with normal blood count in a glucose-6-phosphate dehydrogenase deficient neonate. J Perinatol. 2008;28:306–309
  22. Vreman HJ, Mahoney JJ, Stevenson DK. Carbon monoxide and carboxyhemoglobin. Adv Pediatr. 1995;42:303–334
  23. Katar S. Glucose-6-phosphate dehydrogenase deficiency and kernicterus of South-East Anatolia. J Pediatr Hematol Oncol. 2007;29:284–286
  24. Slusher TM, Vreman HJ, McLaren DW, Lewison LJ, Brown AK, Stevenson DK. Glucose-6-phosphate dehydrogenase deficiency and carboxyhemoglobin concentrations associated with bilirubin-related morbidity and death in Nigerian infants. J Pediatr. 1995;126:102–108
  25. Ogunlesi TA, Dedeke IO, Adekanmbi AF, Fetuga MB, Ogunfowora OB. The incidence and outcome of bilirubin encephalopathy in Nigeria: a bi-centre study. Niger J Med. 2007;16:354–359
  26. Owa JA, Ogunlesi TA. Why we are still doing so many exchange blood transfusions for neonatal jaundice in Nigeria?. World J Pediatr. 2009;5:51–55
  27. Nair PAK, Al Khussiby SM. Kernicterus and G6PD deficiency – a case series from Oman. J Trop Pediatr. 2003;49:74–77
  28. Rehman H, Khan MA, Hameed A, Roghani MT, Ahmad A. Erythrocyte glucose 6 phosphate dehydrogenase deficiency and neonatal jaundice. J Pak Med Assoc. 1995;45:259–260
  29. Wong HB. Singapore kernicterus – the position in 1965. J Singapore Paediatr Soc. 1965;7:35–43
  30. Lai HC, Lai MP, Leung KS. Glucose-6-phosphate dehydrogenase deficiency in Chinese. J Clin Pathol. 1968;21:44–47
  31. Kaplan M, Herschel M, Hammerman C, Hoyer JD, Stevenson DK. Hyperbilirubinemia among African American, glucose-6-phosphate dehydrogenase-deficient neonates. Pediatrics. 2004;114:e213–e219
  32. Chinevere TD, Murray CK, Grant E, Johnson GA, Duelm F, Hospenthal DR. Prevalence of glucose-6-phosphate dehydrogenase deficiency in U.S. Army personnel. Mil Med. 2006;171:905–907
  33. WHO Working Group . Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ. 1989;67:601–611
  34. Fetus and Newborn Committee , Canadian Paediatric Society . Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants (35 or more weeks' gestation). Paediatr Child Health. 2007;12:1B–12B
  35. Profit J, Cambric-Hargrove AJ, Tittle KO, Pietz K, Stark AR. Delayed pediatric office follow-up of newborns after birth hospitalization. Pediatrics. 2009;124:548–554
  36. Kaplan M, Hammerman C, Feldman R, Brisk R. Predischarge bilirubin screening in glucose-6-phosphate dehydrogenase-deficient neonates. Pediatrics. 2000;105:533–537
  37. Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics. 1999;103:6–14
  38. Kaplan M, Vreman HJ, Hammerman C, Leiter C, Abramov A, Stevenson DK. Contribution of haemolysis to jaundice in Sephardic Jewish glucose-6-phosphate dehydrogenase deficient neonates. Br J Haematol. 1996;93:822–827
  39. Kaplan M, Hammerman C, Renbaum P, Levy-Lahad E, Vreman HJ, Stevenson DK. Differing pathogenesis of perinatal bilirubinemia in glucose-6-phosphate dehydrogenase-deficient versus-normal neonates. Pediatr Res. 2001;50:532–537
  40. Kaplan M, Herschel M, Hammerman C, Karrison T, Hoyer JD, Stevenson DK. Studies in hemolysis in glucose-6-phosphate dehydrogenase-deficient African American neonates. Clin Chim Acta. 2006;365:177–182
  41. Muraca M, Blanckaert N. Liquid-chromatographic assay and identification of mono- and diester conjugates of bilirubin in normal serum. Clin Chem. 1983;29:1767–1771
  42. Kaplan M, Rubaltelli FF, Hammerman C, et al. Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency. J Pediatr. 1996;128:695–697
  43. Kaplan M, Muraca M, Hammerman C, et al. Bilirubin conjugation, reflected by conjugated bilirubin fractions, in the pathogenesis of hyperbilirubinemia. Pediatrics. 1998;102:E37
  44. Bosma PJ, Chowdhury JR, Bakker C, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med. 1995;333:1171–1175
  45. Monaghan G, Ryan M, Seddon R, Hume R, Burchell B. Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert's syndrome. Lancet. 1996;347:578–581
  46. Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism?. Proc Natl Acad Sci USA. 1998;95:8170–8174
  47. Kaplan M, Slusher T, Renbaum P, et al. (TA)n UDP-glucuronosyltransferase 1A1 promoter polymorphism in Nigerian neonates. Pediatr Res. 2008;63:109–111
  48. Kaplan M, Renbaum P, Vreman HJ, et al. (TA)n UGT 1A1 promoter polymorphism: a crucial factor in the pathophysiology of jaundice in G-6-PD deficient neonates. Pediatr Res. 2007;61:727–731
  49. Kaplan M, Hammerman C, Maisels MJ. Bilirubin genetics for the nongeneticist: hereditary defects of neonatal bilirubin conjugation. Pediatrics. 2003;111:886–893
  50. Kaplan M, Hammerman C. Bilirubin and the genome: the hereditary basis of unconjugated neonatal hyperbilirubinemia. Curr Pharmacogenomics. 2005;3:21–42
  51. König J, Cui Y, Nies AT, Keppler D. A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. Am J Physiol Gastrointest Liver Physiol. 2000;278:G156–G164
  52. Sanna S, Busonero F, Maschio A, et al. Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia. Hum Mol Genet. 2009;18:2711–2718
  53. Lin Z, Fontaine J, Watchko JF. Coexpression of gene polymorphisms involved in bilirubin production and metabolism. Pediatrics. 2008;122:e156–e162
  54. Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature. 1961;190:372–373
  55. Beutler E, Yeh M, Fairbanks VF. The normal human female as a mosaic of X-chromosome activity: studies using the gene for C-6-PD-deficiency as a marker. Proc Natl Acad Sci USA. 1962;48:9–16
  56. May J, Meyer CG, Grossterlinden L, et al. Red cell glucose-6-phosphate dehydrogenase status and pyruvate kinase activity in a Nigerian population. Trop Med Int Health. 2000;5:119–123
  57. Kaplan M, Beutler E, Vreman HJ, et al. Neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes. Pediatrics. 1999;104:68–74
  58. Kaplan M, Hammerman C, Vreman HJ, Stevenson DK, Beutler E. Acute hemolysis and severe neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes. J Pediatr. 2001;139:137–140
  59. Lim F, Vulliamy T, Abdalla SH. An Ashkenazi Jewish woman presenting with favism. J Clin Pathol. 2005;58:317–319
  60. Herschel M, Ryan M, Gelbart T, Kaplan M. Hemolysis and hyperbilirubinemia in an African American neonate heterozygous for glucose-6-phosphate dehydrogenase deficiency. J Perinatol. 2002;22:577–579
  61. Van Noorden CJ, Vogels IM. A sensitive cytochemical staining method for glucose-6-phosphate dehydrogenase activity in individual erythrocytes. II. Further improvements of the staining procedure and some observations with glucose-6-phosphate dehydrogenase deficiency. Br J Haematol. 1985;60:57–63
  62. Minucci A, Giardina B, Zuppi C, Capoluongo E. Glucose-6-phosphate dehydrogenase laboratory assay: how, when, and why?. IUBMB Life. 2009;61:27–34
  63. Kaplan M, Hoyer JD, Herschel M, Hammerman C, Stevenson DK. Glucose-6-phosphate dehydrogenase activity in term and near-term, male African American neonates. Clin Chim Acta. 2005;355:113–117
  64. Lin Z, Fontaine JM, Freer DE, Naylor EW. Alternative DNA-based newborn screening for glucose-6-phosphate dehydrogenase deficiency. Mol Genet Metab. 2005;86:212–219
  65. Wang FL, Boo NY, Ainoon O, Wong MK. Comparison of detection of glucose-6-phosphate dehydrogenase deficiency using fluorescent spot test, enzyme assay and molecular method for prediction of severe neonatal hyperbilirubinaemia. Singapore Med J. 2009;50:62–67
  66. Kaplan M, Herschel M, Hammerman C, Hoyer JD, Heller GZ, Stevenson DK. Neonatal hyperbilirubinemia in African American males: the importance of glucose-6-phosphate dehydrogenase deficiency. J Pediatr. 2006;149:83–88
  67. Keren R, Luan X, Friedman S, Saddlemire S, Cnaan A, Bhutani VK. A comparison of alternative risk-assessment strategies for predicting significant neonatal hyperbilirubinemia in term and near-term infants. Pediatrics. 2008;121:e170–e179
  68. Kaplan M, Hammerman C. The need for neonatal glucose-6-phosphate dehydrogenase screening: a global perspective. J Perinatol. 2009;29(Suppl. 1):S46–S52
  69. Padilla CD, Therrell BL. Newborn screening in the Asia Pacific region. J Inherit Metab Dis. 2007;30:490–506
  70. Joseph R, Ho LY, Gomez JM, Rajdurai VS, Sivasankaran S, Yip YY. Mass newborn screening for glucose-6-phosphate dehydrogenase deficiency in Singapore. Southeast Asian J Trop Med Public Health. 1999;30(Suppl. 2):70–71
  71. Missiou-Tsagaraki S. Screening for glucose-6-phosphate dehydrogenase deficiency as a preventive measure: prevalence among 1,286,000 Greek newborn infants. J Pediatr. 1991;119:293–299[Missiou-Tsagaraki S. Reply. J Pediatr 1992;12:166]
  72. Mallouh AA, Imseeh G, Abu-Osba YK, Hamdan JA. Screening for glucose-6-phosphate dehydrogenase deficiency can prevent severe neonatal jaundice. Ann Trop Paediatr. 1992;12:391–395

PII: S1744-165X(09)00107-3

doi: 10.1016/j.siny.2009.10.007

Seminars in Fetal & Neonatal Medicine
Volume 15, Issue 3 , Pages 148-156 , June 2010