Familial flavin deficient erythrocytes and malaria susceptibility

KEVIN SALIBA (ANU) in partnership with Frank Mockenhaupt (Charité)


Riboflavin (vitamin B2) is converted into two flavins, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These flavins are essential cofactors for flavoenzymes (flavin-utilising enzymes) such as pyridoxine 5-phosphate oxidase (which uses FMN) and glutathione reductase (which uses FAD). Previous studies [1-4] have shown that there are individuals in Italy that harbour erythrocytes that are flavin-deficient, a condition referred to as Familial Flavin Deficient Erythrocytes (FFDE). It has been hypothesized that this condition has arisen as a result of malaria pressure when the disease was endemic in Italy. The Saliba lab (which has extensive expertise in parasite vitamin requirements [5, 6]) now has unpublished data consistent with a 50% reduction in parasite growth in erythrocytes from individuals with FFDE. The group also has data showing that in vitro flavin depletion of host erythrocytes renders them incapable of supporting parasite growth (even after reintroduction of riboflavin) and that the mechanism may be due to partial resistance to invasion and/or increased sensitivity to oxidative stress by erythrocytes from individuals with FFDE. Furthermore, they have a number of riboflavin analogues that inhibit intraerythrocytic parasite growth by specifically targeting riboflavin metabolism or utilisation by the parasite and/or host erythrocyte.


Interlinkages: Simone Reber (HUB)


References:(1) Anderson, B.B., et al. (1989) Eur. J. Haematol. 42:354-360(2) Anderson, B.B., et al. (1993) Am. J. Clin. Nutr. 57:666-672(3) Anderson, B.B., et al. (1994) Am. J. Hum. Genet. 55:975-980(4) Anderson, B.B., et al. (1995) Am. J. Hum. Genet. 57:674-681