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glucose-6-phosphate dehydrogenase [G6PD] deficiency; chronic non-spherocytic hemolytic anemia (CNSHA)

Classification: 1) Meditarranean variant: - all erythrocytes severely deficient in G6PD 2) A-variant: older erythrocytes express subnormal G6PD Epidemiology: 1) most common enzymatic disorder of erythrocytes 2) 10% of black men 3) 1-50% may carry G6PD-deficient allele in malaria endemic areas [3] Pathology: 1) exposure to oxidative stress results in hemolytic anemia a) oxidative drugs - trimethoprim-sulfamethoxazole - dapsone - primaquine - see pharmaceuticals associated with G6PD hemolytic anemia b) acute illness c) certain foods (fava beans) 2) several types of are recognized [3] a) class-I variants are associated with severe hemolytic anemia b) class-II have an activity of G6PD <10% of normal c) class-III have an activity of G6PD 10%-60% of normal d) class-IV have near normal activity of G6PD 3) hemolytic anemia induces hematopoiesis with reticulocytosis 4) sequestration of damaged erythrocytes in liver & spleen 5) with the A-variant, even with continued drug exposure, acute hemolysis ends after 1 week with reversal of anemia 6) acute hemolysis is more severe with the Mediterranean variant & continues after the drug is discontinued Genetics: - X-linked Clinical manifestations: 1) affected patients are usually asymptomatic 2) hemolytic anemia a) chronic hemolytic anemia b) acute episodes of hemolysis 1] precipitated by: a] acute illness b] exposure to drugs that produce oxidative stress c] certain foods. i.e. fava beans (see favism) 2] occur 2-4 days after drug exposure 3] manifested by mild fever, jaundice, fatigue, pallor, tachycardia, dark red urine and back pain c) A-minus variant results in acute, self-limited hemolysis lasting only a few days d) infection is the most common factor precipitating factor Laboratory: - with acute hemolytic anemia a) peripheral smear: - bite cells (not specific) - Heinz bodies with reticulocyte stains (brilliant cresyl blue) c) urine hemoglobin: hemoglobinuria - G6PD in erythrocytes is low - erythrocyte G6PD should be checked a few months after acute hemolysis [1]* * G6PD is elevated in reticulocytes & levels may appear falsely normal during or shortly after an episode of acute hemolysis [1] Management: 1) supportive therapy a) acute - withdrawal of offending drug(s) - treatment of underlying infection [1] b) chronic - folic acid supplmentation - pneumococcal vaccine - Haemophilus influenzae B vaccine - meningococcal vaccine [1] 2) patients with Mediterranean variant should avoid fava beans 3) affected patients should avoid certain drugs a) sulfa drugs b) primaquine c) nitrofurantoin d) rasburicase [4] (see pharmaceuticals associated with G6PD hemolytic anemia) 4) affected patients should avoid moth balls (naphthalene) & dyes

Related

glucose-6-phosphate 1-dehydrogenase (G6PD) glucose-6-phosphate dehydrogenase (G6PD) in erythrocytes pharmaceutical agents associated with G6PD deficiency hemolytic anemia

Specific

favism

General

enzyme deficiency X-linked disease

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018.
  2. UpToDate 13.2
  3. UniProt :accession P11413
  4. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008 Jan 5;371(9606):64-74. PMID: 18177777
  5. Relling MV, McDonagh EM, Chang T et al Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clin Pharmacol Ther. 2014 Aug;96(2):169-74. PMID: 24787449
  6. Luzzatto L, Arese P Favism and Glucose-6-Phosphate Dehydrogenase Deficiency. N Engl J Med 2018; 378:60-71. January 4, 2018 PMID: 29298156 http://www.nejm.org/doi/full/10.1056/NEJMra1708111
  7. Luzzatto L, Seneca E G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications. Br J Haematol. 2014 Feb;164(4):469-80. Epub 2013 Dec 28. Review. PMID: 24372186 Free PMC Article
  8. ARUP Consult: Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency https://arupconsult.com/ati/glucose-6-phosphate-dehydrogenase-deficiency