Pyruvate Kinase Deficiency and Malaria

• Published in: The New England journal of medicine Vol. 358; no. 17; pp. 1805 - 1810
• Main Authors: Ayi, Kodjo, Min-Oo, Gundula, Serghides, Lena, Crockett, Maryanne, Kirby-Allen, Melanie, Quirt, Ian, Gros, Philippe, Kain, Kevin C
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 24.04.2008
• Subjects: Adult; Animals; Biological and medical sciences; Erythrocytes - enzymology; Erythrocytes - parasitology; Female; General aspects; Genetic Predisposition to Disease; Human protozoal diseases; Humans; Infectious diseases; Malaria; Malaria, Falciparum - blood; Malaria, Falciparum - enzymology; Malaria, Falciparum - genetics; Male; Medical sciences; Mutation; Parasitic diseases; Phagocytosis; Plasmodium falciparum; Polymorphism, Single Nucleotide; Protozoal diseases; Pyruvate Kinase - deficiency; Pyruvate Kinase - genetics; Infection; Medicine; Protozoal disease; Hemolytic anemia; Malaria; Pyruvate kinase deficiency; Metabolic diseases; Hemopathy; Parasitosis; Enzymopathy; Genetic disease
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa072464

Erythrocytes from patients with pyruvate kinase deficiency are resistant to invasion by Plasmodium falciparum . Such erythrocytes that succumb to infection are more rapidly cleared by macrophages than are infected erythrocytes from control subjects. These data suggest that mutations in the gene encoding pyruvate kinase may confer resistance to malaria. Erythrocytes from patients with pyruvate kinase deficiency are resistant to invasion by Plasmodium falciparum . These data suggest that mutations in the gene encoding pyruvate kinase may confer resistance to malaria. Malaria is an important parasitic disease in humans, causing an estimated 500 million clinical cases and more than 1 million deaths annually. 1 Disease control has been hampered by drug resistance in plasmodium parasites and by the lack of an effective vaccine. 2 , 3 A better understanding of the pathogenesis of malaria, including the identification of innate or adaptive host defense mechanisms against the blood-stage parasite, may provide new targets for intervention in this disease. Such mechanisms may be manifested as genetic determinants of susceptibility in areas of endemic disease and during epidemics and as variations according to strain in mouse models . . .