Glucose-6-Phosphate Dehydrogenase Deficiency 

  • Author: Suzanne M Carter, MS; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Jan 10, 2012
 

Background

Glucose-6-phosphatase dehydrogenase (G6PD) deficiency is the most common disease-producing enzymopathy in humans. Inherited as an X-linked disorder, glucose-6-phosphatase dehydrogenase (G6PD) deficiency affects 400 million people worldwide. The disease is highly polymorphic, with more than 300 reported variants. It confers protection against malaria, which probably accounts for its high gene frequency.[1, 2] See image below.

Heinz bodies. Acute hemolysis from glucose-6-phospHeinz bodies. Acute hemolysis from glucose-6-phosphatase dehydrogenase deficiency is linked to the development of Heinz bodies, which are composed of denatured hemoglobin.

For excellent patient education resources, visit eMedicine's Children's Health Center. Also, see eMedicine's patient education article Newborn Jaundice.

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Pathophysiology

The G6PD enzyme catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconate while concomitantly reducing the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP+) to nicotinamide adenine dinucleotide phosphate (NADPH). NADPH, a required cofactor in many biosynthetic reactions, maintains glutathione in its reduced form.

Reduced glutathione acts as a scavenger for dangerous oxidative metabolites in the cell. With the help of the enzyme glutathione peroxidase, reduced glutathione also converts harmful hydrogen peroxide to water. Red blood cells rely heavily upon glucose-6-phosphatase dehydrogenase (G6PD) activity because it is the only source of NADPH that protects the cells against oxidative stresses; therefore, people deficient in glucose-6-phosphatase dehydrogenase (G6PD) are not prescribed oxidative drugs, because their red blood cells undergo rapid hemolysis under this stress.

The 5 classes of glucose-6-phosphatase dehydrogenase (G6PD) deficiency include low, normal, or increased levels of the enzyme.

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Epidemiology

Frequency

International

The highest prevalence rates (with gene frequencies from 5-25%) of glucose-6-phosphatase dehydrogenase (G6PD) deficiency are found in tropical Africa, the Middle East, tropical and subtropical Asia, some areas of the Mediterranean, and Papua New Guinea.[3, 4, 5]

Mortality/Morbidity

The most common clinical feature of glucose-6-phosphatase dehydrogenase (G6PD) deficiency is a lack of symptoms. Symptomatic patients present with neonatal jaundice and acute hemolytic anemia.

  • Neonatal jaundice: Jaundice usually appears by age 1-4 days, at the same time as or slightly earlier than so-called physiologic jaundice and later than in in-blood group alloimmunization.[6, 7] Kernicterus is a rare complication.[8]
  • Acute hemolytic anemia: Clinical expression results from stress factors such as oxidative drugs or chemicals, infection, or ingestion of fava beans.[3, 4, 9, 10]

Race

Glucose-6-phosphatase dehydrogenase (G6PD) deficiency affects all races. The highest prevalence is among persons of African, Asian, or Mediterranean descent.[3, 4] The severity of glucose-6-phosphatase dehydrogenase (G6PD) deficiency varies significantly among racial groups because of different variants of the enzyme. Severe deficiency variants primarily occur in the Mediterranean population. The enzymatic variants in the African population have more activity and produce a milder form of the disease.

Sex

  • Glucose-6-phosphatase dehydrogenase (G6PD) deficiency is an X-linked inherited disease that primarily affects men.
  • Homozygous women are found in populations in which the frequency of glucose-6-phosphatase dehydrogenase (G6PD) deficiency is quite high.
  • Heterozygous (carrier) women can develop hemolytic attacks.
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Contributor Information and Disclosures
Author

Suzanne M Carter, MS  Senior Genetic Counselor, Associate, Department of Obstetrics and Gynecology, Division of Reproductive Genetics, Montefiore Medical Center, Albert Einstein College of Medicine

Suzanne M Carter, MS is a member of the following medical societies: American Bar Association

Disclosure: Nothing to disclose.

Coauthor(s)

Susan J Gross, MD, FRCS(C), FACOG, FACMG  Codirector, Division of Reproduction Genetics, Associate Professor, Department of Obstetrics and Gynecology, Albert Einstein College of Medicine

Susan J Gross, MD, FRCS(C), FACOG, FACMG is a member of the following medical societies: American College of Medical Genetics, American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, American Society of Human Genetics, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Specialty Editor Board

Karen Seiter, MD  Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching; Novartis Consulting fee Speaking and teaching; Eisai Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Marcel E Conrad, MD  Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

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  2. Peters AL, Van Noorden CJ. Glucose-6-phosphate Dehydrogenase Deficiency and Malaria: Cytochemical Detection of Heterozygous G6PD Deficiency in Women. J Histochem Cytochem. Jun 22 2009;[Medline].

  3. Beutler E. Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med. Jan 17 1991;324(3):169-74. [Medline].

  4. Beutler E. G6PD deficiency. Blood. Dec 1 1994;84(11):3613-36. [Medline]. [Full Text].

  5. Nkhoma ET, Poole C, Vannappagari V, et al. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol Dis. May-Jun 2009;42(3):267-78. [Medline].

  6. Valaes T, Drummond GS, Kappas A. Control of hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient newborns using an inhibitor of bilirubin production, Sn-mesoporphyrin. Pediatrics. May 1998;101(5):E1. [Medline]. [Full Text].

  7. 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. Jul 2001;139(1):137-40. [Medline].

  8. Kaplan M, Hammerman C. Glucose-6-phosphate dehydrogenase deficiency: a hidden risk for kernicterus. Semin Perinatol. Oct 2004;28(5):356-64. [Medline].

  9. McDade J, Abramova T, Mortier N, Howard T, Ware RE. A novel G6PD mutation leading to chronic hemolytic anemia. Pediatr Blood Cancer. Dec 2008;51(6):816-9. [Medline].

  10. Ozbay Hosnut F, Ozcay F, et al. Etiology of hemolysis in two patients with hepatitis A infection: glucose-6-phosphate dehydrogenase deficiency or autoimmune hemolytic anemia. Eur J Pediatr. Dec 2008;167(12):1435-9. [Medline].

  11. Yang Y, Li Z, Nan P, Zhang X. Drug-induced glucose-6-phosphate dehydrogenase deficiency-related hemolysis risk assessment. Comput Biol Chem. Jun 2011;35(3):189-92. [Medline].

  12. Minucci A, Giardina B, Zuppi C, Capoluongo E. Glucose-6-phosphate dehydrogenase laboratory assay: How, when, and why?. IUBMB Life. Oct 21 2008;[Medline].

  13. Wang FL, Boo NY, Ainoon O, et al. 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. Jan 2009;50(1):62-7. [Medline].

  14. Mesner O, Hammerman C, Goldschmidt D, et al. Glucose-6-phosphate dehydrogenase activity in male premature and term neonates. Arch Dis Child Fetal Neonatal Ed. Nov 2004;89(6):F555-7. [Medline]. [Full Text].

  15. Murki S, Dutta S, Narang A, Sarkar U, Garewal G. A randomized, triple-blind, placebo-controlled trial of prophylactic oral phenobarbital to reduce the need for phototherapy in G6PD-deficient neonates. J Perinatol. May 2005;25(5):325-30. [Medline].

  16. Samanta S, Kumar P, Kishore SS, et al. Donor blood glucose 6-phosphate dehydrogenase deficiency reduces the efficacy of exchange transfusion in neonatal hyperbilirubinemia. Pediatrics. Jan 2009;123(1):e96-e100. [Medline].

  17. Beutler E, Westwood B, Prchal JT, et al. New glucose-6-phosphate dehydrogenase mutations from various ethnic groups. Blood. Jul 1 1992;80(1):255-6. [Medline]. [Full Text].

  18. Sklar GE. Hemolysis as a potential complication of acetaminophen overdose in a patient with glucose-6-phosphate dehydrogenase deficiency. Pharmacotherapy. May 2002;22(5):656-8. [Medline].

  19. Valiaveedan S, Mahajan C, Rath GP, Bindra A, Marda MK. Anaesthetic management in patients with glucose-6-phosphate dehydrogenase deficiency undergoing neurosurgical procedures. Indian J Anaesth. Jan 2011;55(1):68-70. [Medline]. [Full Text].

 
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Heinz bodies. Acute hemolysis from glucose-6-phosphatase dehydrogenase deficiency is linked to the development of Heinz bodies, which are composed of denatured hemoglobin.
 
 
 
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