eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Glucose-6-Phosphate Dehydrogenase Deficiency

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
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
Contributor Information and Disclosures

Updated: Nov 13, 2008

Introduction

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.

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

Related eMedicine topics:
Glucose-6-Phosphatase Deficiency [in the Endocrinology section]
Hemolytic Disease of Newborn
Kernicterus
Methemoglobinemia

Related Medscape topics:
Resource Center Genomic Medicine
Specialty Site Diabetes & Endocrinology
Specialty Site Hematology-Oncology
Specialty Site Pediatrics
CME/CE New Recommendations Issued for Treatment of Malaria in the United States Dried Blood Spots as a Source of Anti-malarial Antibodies for Epidemiological Studies FDA Releases List of Genomic Biomarkers Predictive of Drug Interactions
Hemolysis and Failed Hematopoiesis (Slides With Transcript)

Malaria in Refugees From Tanzania -- King County, Washington, 2007

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.

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.1,2

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.3,4 Kernicterus is a rare complication.5
  • Acute hemolytic anemia: Clinical expression results from stress factors such as oxidative drugs or chemicals, infection, or ingestion of fava beans.1,2

Related Medscape topics:
Resource Center Neonatal Medicine
Specialty Site Gastroenterology

Race

Glucose-6-phosphatase dehydrogenase (G6PD) deficiency affects all races. The highest prevalence is among persons of African, Asian, or Mediterranean descent.1,2 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.

Clinical

History

Most patients with glucose-6-phosphatase dehydrogenase (G6PD) deficiency are asymptomatic. Some patients present with or report a history of neonatal jaundice, often requiring exchange transfusion. A history of infection or drug-induced hemolysis is also common. Gallstones may be a prominent feature. Splenomegaly may be present.

Related Medscape topics:
Resource Center Adverse Drug Events Reporting
Resource Center Sepsis

Physical

Jaundice and splenomegaly may be present during a glucose-6-phosphatase dehydrogenase (G6PD) deficiency crisis.

Causes

Glucose-6-phosphatase dehydrogenase (G6PD) deficiency is a genetic condition. The molecular basis for this disease results from mutations in the G6PD locus at Xq28. The gene is 18 kilobases (kb) long with 13 exons, leading to an enzyme of 515 amino acids. More than 60 mutations in the G6PD gene have been documented; most of the mutations are single-base changes that result in an amino acid substitution.

More on Glucose-6-Phosphate Dehydrogenase Deficiency

Overview: Glucose-6-Phosphate Dehydrogenase Deficiency
Differential Diagnoses & Workup: Glucose-6-Phosphate Dehydrogenase Deficiency
Treatment & Medication: Glucose-6-Phosphate Dehydrogenase Deficiency
Follow-up: Glucose-6-Phosphate Dehydrogenase Deficiency
Multimedia: Glucose-6-Phosphate Dehydrogenase Deficiency
References

References

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

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

  3. 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].

  4. 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].

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

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

  7. 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].

  8. 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].

  9. Au WY, Pang A, Lam KK, et al. G6PD deficiency from lyonization after hematopoietic stem cell transplantation from female heterozygous donors. Bone Marrow Transplant. Oct 2007;40(7):677-81. [Medline].

  10. Beutler E. Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. Blood. Jan 1 2008;111(1):16-24. [Medline][Full Text].

  11. 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].

  12. 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].

  13. 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].

  14. 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].

Further Reading

Keywords

glucose-6-phosphatase dehydrogenase deficiency, G6PD, G6PD deficiency, G-6-PD deficiency, acute hemolytic anemia, glucosephosphate dehydrogenase deficiency, GPD deficiency, X-linked disorders, nicotinamide adenine dinucleotide phosphate, NADP+, nicotinamide adenine dinucleotide phosphate, NADPH, enzyme deficiency, chronic nonspherocytic hemolytic anemia, neonatal jaundice, fava beans, favism, enzymopathy

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.

Medical Editor

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; Celgene Honoraria Speaking and teaching; Schering Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, 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, 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 Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.