Glucose 6-phosphate dehydrogenase, deficiency

Favism is the haemolysis obseived after eating Vica fava. This reaction is observed in individuals with glucose-6-phosphate dehydrogenase deficiency. This common deficiency is also responsible for haemolysis in response to the antimalarial drug primaquine and others. 

An idiosyncratic reaction is a harmful, sometimes fatal reaction, that occurs in a small minority of individuals. The reaction may occur with low doses of drags. Genetic factors may be responsible, e.g. glucose-6-phosphate dehydrogenase deficiency, although the cause is often poorly understood. 

Raupp, R, et al.. Henna causes life threatening haemolysis in glucose-6-phosphate dehydrogenase deficiency. Arch. Dis. Child., 85, 411, 2001. 

When advising potential travelers on prophylaxis for malaria, be aware of the incidence of chloroquine-resistant P. falciparum malaria and the countries where it is prevalent. In patients who have P. vivax or P. ovale malaria (note that some patients can have P. falciparum and one of these species), following the treatment of the acute phase of malaria and screening for glucose-6-phosphate dehydrogenase deficiency, patients should receive a regimen of primaquine for 14 days to ensure eradication of the hypnozoite stage of P. vivax or P. ovale. For detailed recommendations for prevention of malaria go to www.cdc.gov/travel/. 

Since the discovery of glucose-6-phosphate dehydrogenase deficiency (C3) and... 

B20. Beutler, E., Glucose-6-phosphate dehydrogenase deficiency. New Engl. J. Med. 324, 169-174... 

CL Calabro, V., Mason, P. J., Filosa, S Civitelli, D., Cittadella, R.,Tagarclli, A., Martini, G., Bran-cati, C., and Luzzatto, L., Genetic heterogeneity of glucose-6-phosphate dehydrogenase deficiency revealed by single-strand conformation and sequence analysis. Am. J. Hum. Genet. 52, 527-536(1993). 

G2. Ganczakowski, M., Town, M., Bowden, D. K Vulliamy, T. J., Kaneko, A., Clegg, J. B., Weatherall, D. J., and Luzzatto, L Multiple glucose 6-phosphate dehydrogenase-deficient variants correlate with malaria endemicity in the Vanuatu archipelago (southwestern Pacific). Am. J. Hum. Genet. 56,294-301 (1995). 

H13. Hirono, A., Miwa, S., Fujii, H Ishida, F., Yamada, K., and Kubota, K., Molecular study of eight Japanese cases of glucose-6-phosphate dehydrogenase deficiency by non-radioisotopic singlestrand conformation polymorphism (SSCP) analysis. Blood 83,3363-3368 (1994). 

Cocco P, Carta P, Flore C, et al. 1996. Mortality of lead smelter workers with the glucose-6-phosphate dehydrogenase-deficient phenotype. Cancer Epidemiol Biomarkers Prev 5(3) 223-225. 

Cocco PL, Cocco E, Anni MS, et al. 1991. Occupational exposure to lead and blood cholesterol in glucose-6-phosphate dehydrogenase deficient and normal subjects. Res Commun Chem Pathol Pharmacol 72(1) 81-95. 

Primaquine should be administered cautiously to actually ill patients with any serious systemic disease characterized by a tendency to granulocytopenia such as rheumatoid arthritis or lupus erythematosus. The drug should be used with care in patients with glucose-6-phosphate dehydrogenase deficiency. Primaquine should be withdrawn if signs of haemolysis or methaemoglobinaemia occur and the blood... 

The answers are 484-k 485-j. (tlardman, pp 1061-1062, 1682-1685.) Sulfonamides can cause acute hemolytic anemia. In some patients it mayr be related to a sensitization phenomenon, and in other patients the hemolysis is due to a glucose-6-phosphate dehydrogenase deficiency Sulfamethoxazole alone or in combination with trimethoprim is used to treat UTls. The sulfonamide sulfasalazine is employed in the treatment of ulcerative colitis. Daps one, a drug that is used in the treatment of leprosy, and primaquine, an anti mala rial agent, can produce hemolysis, particularly in patients with a glucose-6-phosphate dehydrogenase deficiency. 

Hemolytic anemia results from decreased RBC survival time due to destruction in the spleen or circulation. The most common etiologies are RBC membrane defects (e.g., hereditary spherocytosis), altered Hb solubility or stability (e.g., sickle cell anemia [see Chap. 34] and thalassemias), and changes in intracellular metabolism (e.g., glucose-6-phosphate dehydrogenase deficiency). Some drugs cause direct oxidative damage to RBCs (see Appendix 3). 

Treatment of hemolytic anemia should focus on correcting the underlying cause. There is no specific therapy for glucose-6-phosphate dehydrogenase deficiency, so treatment consists of avoiding oxidant medications and chemicals. Steroids, other immunosuppressants, and even splenectomy can be indicated to reduce RBC destruction. 

Luzzatto, L., and A. Mehta, "Glucose 6-Phosphate Dehydrogenase Deficiency," In Scriver CR et al. (eds), The Metabolic and Molecular Bases of Inherited Disease, 7th ed. New York McGraw-Hill (1995). 

G6. Gilles, H. M., and Ikeme, A. C., Hemoglobinuria among adult Nigerians due to glucose-6-phosphate dehydrogenase deficiency with drug sensitivity. Lancet i, 889-891 (1960). 

C18. Cross, R. T., Hurwitz, R. E., and Marks, P. A., An hereditary enzymatic defect in erythrocyte metabolism Glucose-6-phosphate dehydrogenase deficiency. J. Clin. Invest. 37, 1170-1184 (1958). 

R5. Ramot, B., Sheba, C., Adam, A., and Ashkenazi, I., Erythrocyte glucose-6-phosphate dehydrogenase deficient subjects Enzyme level in saliva. Nature 185, 931 (1960). 

Ulcerative colitis Inform patients with this condition that ulcerative colitis rarely remits completely, and that the risk of relapse can be substantially reduced by continued administration of sulfasalazine at a maintenance dosage. Glucose-6-phosphate dehydrogenase deficiency Observe patients with glucose-6-phosphate dehydrogenase deficiency closely for signs of hemolytic anemia. This reaction is frequently dose-related. 

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