You are in: eMedicine Specialties > Hematology > Red Blood Cells and Disorders Glucose-6-Phosphate Dehydrogenase DeficiencyArticle Last Updated: Aug 29, 2005AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  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 is a member of the following medical societies: American Bar Association 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 Editors: Karen Seiter, MD, Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Marcel E Conrad, MD, BS, (Retired) Distinguished Professor of Medicine, University of South Alabama; Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems; Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University Author and Editor Disclosure Synonyms and related keywords: G-6-PD deficiency, X-linked disorders, nicotinamide adenine dinucleotide phosphate, NADP+, nicotinamide adenine dinucleotide phosphate, NADPH, enzyme deficiency, chronic nonspherocytic hemolytic anemia, neonatal jaundice, acute hemolytic anemia, fava beans, favism, enzymopathy INTRODUCTIONSection 2 of 11
  BackgroundGlucose-6-phosphatase dehydrogenase (G-6-PD) deficiency is the most common disease-producing enzymopathy in humans. Inherited as an X-linked disorder, G-6-PD 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. PathophysiologyThe 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 G-6-PD activity because it is the only source of NADPH that protects the cells against oxidative stresses; therefore, people deficient in G-6-PD are not prescribed oxidative drugs because their red blood cells undergo rapid hemolysis under this stress. The five classes of G-6-PD deficiency include low, normal, or increased levels of the enzyme. FrequencyInternationalThe highest prevalence rates (with gene frequencies from 5-25%) are found in tropical Africa, the Middle East, tropical and subtropical Asia, some areas of the Mediterranean, and Papua New Guinea. Mortality/MorbidityThe most common clinical feature is a lack of symptoms. Symptomatic patients present with neonatal jaundice and acute hemolytic anemia.
RaceG-6-PD deficiency affects all races. The highest prevalence is among persons of African, Asian, or Mediterranean descent. Severity varies significantly between 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
CLINICALSection 3 of 11
HistoryMost patients 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. PhysicalJaundice and splenomegaly may be present during a crisis. CausesG-6-PD deficiency is a genetic condition. The molecular basis for G-6-PD deficiency results from mutations in the G6PD locus at Xq28. The gene is 18 kilobases long with 13 exons, leading to an enzyme of 515 amino acids. Most of the mutations are single-base changes that result in an amino acid substitution. DIFFERENTIALSSection 4 of 11
Hemolytic Anemia Sickle Cell Anemia Spherocytosis, Hereditary WORKUPSection 5 of 11
Lab Studies
Imaging Studies
Histologic FindingsAcute hemolysis from G-6-PD deficiency is associated with formation of Heinz bodies, which consist of denatured hemoglobin. TREATMENTSection 6 of 11
Medical CareIdentification and discontinuation of the precipitating agent is critical. Individuals are treated with oxygen and bed rest, which may afford symptomatic relief. Consultations
DietPatients must avoid broad beans (ie, fava beans). Favism occurs only in the Mediterranean variety of G-6-PD deficiency. ActivityCurtailment of physical activity may be necessary if severe anemia results from hemolysis. MEDICATIONSection 7 of 11
The data show that jaundice in G6PD-deficient neonates is the result of an imbalance between production and conjugation of bilirubin with a tendency for inefficient bilirubin conjugation over increased hemolysis in its pathogenesis. Borderline premature infants are at special risk of bilirubin production-conjugation imbalance. Prophylactic oral phenobarbital does not decrease the need for phototherapy or exchange transfusions in G6PD-deficient neonates. FOLLOW-UPSection 8 of 11
Further Inpatient Care
In/Out Patient Meds
Deterrence/Prevention
Complications
Prognosis
Patient Education
MISCELLANEOUSSection 9 of 11
Medical/Legal Pitfalls
Special Concerns
MULTIMEDIASection 10 of 11
REFERENCESSection 11 of 11
Glucose-6-Phosphate Dehydrogenase Deficiency excerpt Article Last Updated: Aug 29, 2005 | ||||||||||||||
