18-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. 

Inherited defects in the enzymes of (3-oxidation and ketogenesis also lead to nonketotic hypoglycemia, coma, and fatty hver. Defects are known in long- and short-chain 3-hydroxyacyl-CoA dehydrogenase (deficiency of the long-chain enzyme may be a cause of acute fetty liver of pr nancy). 3-Ketoacyl-CoA thiolase and HMG-CoA lyase deficiency also affect the degradation of leucine, a ketogenic amino acid (Chapter 30). 

Treem WR et al Acute fatty liver of pregnancy and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. Hepatology 1994 19 339. 

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/. 

Deficiencies of enzymes involved in glycolysis, the hexose monophosphate pathway, the closely related glutathione metabolism and synthesis, and nucleotide metabolism have emerged as causes of hereditary nonspherocytic hemolytic anemias (Table 1) (F10, Fll, M27). Some enzyme deficiencies, such as diphospho-glycerate mutase deficiency, lactate dehydrogenase deficiency, and NADH cy-... 

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... 

Harris BE, Carpenter JT, Diasio RB. Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common phar-macogenetic syndrome. Cancer 1991 68 499-501. 

Milano G, Etienne MC, Pierrefite V et al. Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. Br J Cancer 1999 79 627-630. 

Wei X, McLeod HL, McMurrough J et al. Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. J Clin Invest 1996 98 610-615. 

Johnson MR, Hageboutros A, Wang K et al. life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. Clin Cancer Res 1999 5 2006-2011. 

Crabb DW, Edenberg HJ, Bosron WF, Li T-K. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2 2 allele is dominant. J Clin Invest 1989 83 314—316. 

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. 

Succinic semialdehyde dehydrogenase deficiency. Patients have mental retardation, cerebellar disease, and hypotonia. They excrete large amounts of both succinic semialdehyde and 4-hydroxybutyric acid. There is no known therapy. 

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