Hyperphenylalaninaemia in children with falciparum malaria

Brain monoamine levels may underlie aspects of the cerebral component of fa lciparum malaria. Since circulating amino acids are the precursors for brai n monoamine synthesis, we measured them in malaria patients and controls. M alaria elicited significantly elevated plasma levels of phenylalanine, part icularly in comatose patients, with the Tyr/Phe (%) ratio reduced from 83.3 in controls to 39.5 in infected children, suggesting an impaired phenylala nine hydroxylase enzyme system in malaria infection. Malaria significantly increased the apparent K-m for Trp, Tyr and His, with no effect on K-m(app) for Phe. Using the kinetic parameters of NAA transport at the human blood- brain barrier, malaria significantly altered brain uptake of Phe (+96%), Tr p (-28%) and His (+31%), with no effect on Tyr (-8%), compared with control findings. Our data suggest impaired cerebral synthesis of serotonin, dopam ine and norepinephrine, and enhanced production of histamine, in children w ith severe falciparum malaria.