Altered 5-aminolevulinic acid metabolimn leading to pseudoporphyria in hemodialysed patients

Abstract

Hemodiaiysed patients with no history of porphyna may present neurological symptoms molar to those seen in acute porphyrias. Porpbyria her been associated with an increase in plasma levels of 5-aminolevulinic acid and porphobilinogen. Our aim was to evaluate these parameters and the activities of the enzymes involved in the first steps of heme metabolism in non-porphyric hemodialysed patients. The activities of 5-aminolevulinate dehydratase and deaminsue were determined in red blood cells (RBC) from 78 hemodialysed patients, before and after dialysis. Plasma levels of 5-aminolevulinic acid, porphobilinogen and zinc were also measured. These parameters were also measured in 40 volunteers to obtain controls levels. The levels of 5-aailstdevoBnic acid (0.98 ± 0.09 μg/ml) and porphobilinogen (1.32 ± 0.13 μg/ml) were raised in non-porpbyric patients prior to hemodiayysis ( P < 0.001) compared with controls (5aminolevalinic acid 0.13 ± 0.02 μg/ml; porphobilinogen 0.90 ± 0.09 μg/ml). After dialysis mere was a decrease in both 5-aminolevulinic acid (to 0.61 ± 0.05 μg/ml) and porpliobillnogen (to 1.10 ± 0.16 μg/ml) although both parameters remained higher than controls ( P < 0.001). The activities of both 5-aminolevulinate dehydratase (0.550 ± 0.095 U/ml RBC), and deamium (54.13 ± 9.13 U/ml RBC) were diminished in blood samples of patients before dialysis ( P < 0.001) compared to controls (dehydratase 0.975 ± 0.115 U/ml RBC; deaminese 77.32 ± 10.00 U/ml RBC). After dialysis 5-aminolevulinate dehydratase activity was partially recovered (to 0.666 ± 0.100 U/ml RBC) while deaminase returned to normal values (73.45 ± 9.46 U/ml RBC). The plasma zinc concentration in hemodialysed patients (44 ± 12 pg/100 ml) was significantly lower than controls (105 ± 30 μg/100 ml, P < 0.001). Addition of 22.5 MM zinc to the dehydratase reaction mixture raised the activity of 5-aminolevulinate dehydratase in blood samples of hemodialysed patients taken before and after dialysis. The study reports a partial loss of activity of 5-amloolevnlinate dehydratase and deaminase activities in red blood cells from non-porpbyric patients undergoing hemodialysis . Since plasma zinc levels were below normal in hemodialysed patients, and the activity of 5-aminolevulinate dehydmtme could be restored by the addition of zinc, it is suggested that these abnormalities in hence metabolism may be explained by altered zinc and associated antioxidant status following dialysis.