glucose-6-phosphate dehydrogenase [G6PD] deficiency; chronic non-spherocytic hemolytic anemia (CNSHA)
Jump to navigation
Jump to search
Classification
- Meditarranean variant:
- all erythrocytes severely deficient in G6PD
- A-variant: older erythrocytes express subnormal G6PD
Epidemiology
- most common enzymatic disorder of erythrocytes
- 10% of black men
- 1-50% may carry G6PD-deficient allele in malaria endemic areas[3]
Pathology
- exposure to oxidative stress results in hemolytic anemia
- oxidative drugs
- trimethoprim-sulfamethoxazole
- dapsone
- primaquine
- see pharmaceuticals associated with G6PD hemolytic anemia
- acute illness
- certain foods (fava beans)
- oxidative drugs
- several types of are recognized[3]
- class-I variants are associated with severe hemolytic anemia
- class-II have an activity of G6PD <10% of normal
- class-III have an activity of G6PD 10%-60% of normal
- class-IV have near normal activity of G6PD
- hemolytic anemia induces hematopoiesis with reticulocytosis
- sequestration of damaged erythrocytes in liver & spleen
- with the A-variant, even with continued drug exposure, acute hemolysis ends after 1 week with reversal of anemia
- acute hemolysis is more severe with the Mediterranean variant & continues after the drug is discontinued
Genetics
Clinical manifestations
- affected patients are usually asymptomatic
- hemolytic anemia
- chronic hemolytic anemia
- acute episodes of hemolysis
- precipitated by:
- acute illness
- exposure to drugs that produce oxidative stress
- certain foods. i.e. fava beans (see favism)
- occur 2-4 days after drug exposure
- manifested by mild fever, jaundice, fatigue, pallor, tachycardia, dark red urine and back pain
- precipitated by:
- A-minus variant results in acute, self-limited hemolysis lasting only a few days
- infection is the most common factor precipitating factor
Laboratory
- with acute hemolytic anemia
- peripheral smear:
- bite cells (not specific)
- Heinz bodies with reticulocyte stains (brilliant cresyl blue)
- urine hemoglobin: hemoglobinuria
- peripheral smear:
- 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
- supportive therapy
- acute
- withdrawal of offending drug(s)
- treatment of underlying infection[1]
- chronic
- folic acid supplmentation
- pneumococcal vaccine
- Haemophilus influenzae B vaccine
- meningococcal vaccine[1]
- acute
- patients with Mediterranean variant should avoid fava beans
- affected patients should avoid certain drugs
- sulfa drugs
- primaquine
- nitrofurantoin
- rasburicase[4] (see pharmaceuticals associated with G6PD hemolytic anemia)
- affected patients should avoid moth balls (naphthalene) & dyes
More general terms
More specific terms
Additional terms
- glucose-6-phosphate 1-dehydrogenase (G6PD)
- glucose-6-phosphate dehydrogenase (G6PD) in erythrocytes
- pharmaceutical agents associated with G6PD deficiency hemolytic anemia
References
- ↑ Jump up to: 1.0 1.1 1.2 1.3 1.4 Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018.
- ↑ UpToDate 13.2
- ↑ Jump up to: 3.0 3.1 3.2 UniProt http://www.uniprot.org/uniprot/P11413.html
- ↑ Jump up to: 4.0 4.1 Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008 Jan 5;371(9606):64-74. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18177777
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/24787449
- ↑ Luzzatto L, Arese P Favism and Glucose-6-Phosphate Dehydrogenase Deficiency. N Engl J Med 2018; 378:60-71. January 4, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29298156 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMra1708111
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/24372186 Free PMC Article
- ↑ ARUP Consult: Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency https://arupconsult.com/ati/glucose-6-phosphate-dehydrogenase-deficiency