Manifestation of hereditary fructose intolerance.

Death from P. falciparum infection in subjects who live in areas of stable malaria is usually due either to cerebral involvement or to the consequences of anaemia (Edington and Gilles, 1969). Almost all the data on increased resistance against malaria have been obtained in A/S heterozygotes, and there is no a priori reason to expect that they should apply to S/S homozygotes. In addition, one can envisage some mechanisms whereby malaria might actually lead to death in the homozygote. (1) A patient with sicklecell disease suffers from chronic anaemia. The superimposed haemolysis from acute malaria infection may precipitate anaemic heart failure. This occurred in our case. (2) Malaria might act as a trigger for intravascular sickling (Edington, 1953). Parasitized cells from A/S heterozygotes tend to sickle more readily than non-parasitized cells (Luzzatto et al., 1970), a phenomenon which facilitates their trapping by a normal reticuloendothelial system. However, when a major component of that system, the spleen, is atrophied as a result of sickle-cell disease (as in our patient), parasitized cells will continue to circulate and the parasitaemia may threaten life. In conclusion, we suggest that in our case, and in that of Rey et al. (1966), the S gene in double dose failed to protect against severe malaria and the peculiar interaction between this genetic abnormality and malarial infection led to the fatal outcome.