title: Altered 5-aminolevulinic acid metabolism leading to pseudoporphyria in hemodialysed patients.
abstract: Hemodialysed patients with no history of porphyria may present neurological symptoms similar to those seen in acute porphyrias. Porphyria has 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 deaminase 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-aminolevulinic acid (0.98 +/- 0.09 microgram/ml) and porphobilinogen (1.32 +/- 0.13 micrograms/ml) were raised in non-porphyric patients prior to hemodialysis (P < 0.001) compared with controls (5-aminolevulinic acid 0.13 +/- 0.02 microgram/ml; porphobilinogen 0.90 +/- 0.09 microgram/ml). After dialysis there was a decrease in both 5-aminolevulinic acid (to 0.61 +/- 0.05 microgram/ml) and porphobilinogen (to 1.10 +/- 0.16 micrograms/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 deaminase (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; deaminase 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 micrograms/100 ml) was significantly lower than controls (105 +/- 30 micrograms/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-aminolevulinate dehydratase and deaminase activities in red blood cells from non-porphyric patients undergoing hemodialysis. Since plasma zinc levels were below normal in hemodialysed patients, and the activity of 5-aminolevulinate dehydratase could be restored by the addition of zinc, it is suggested that these abnormalities in heme metabolism may be explained by altered zinc and associated antioxidant status following dialysis.
authors.affiliation: Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), Universidad de Buenos Aires, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Guolo
authors.forename: A M
authors.initials: AM
authors.lastname: Stella
authors.forename: V
authors.initials: V
authors.lastname: Melito
authors.forename: V
authors.initials: V
authors.lastname: Parera
authors.forename: A M
authors.initials: AM
authors.lastname: Del C Batlle
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006358:Hot Temperature; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011162:Porphobilinogen / Q000097:blood; D000623:Porphobilinogen Synthase / Q000097:blood*; D011164:Porphyrias / Q000209:etiology / Q000378:metabolism*; D006435:Renal Dialysis / Q000009:adverse effects*; D015032:Zinc / Q000097:blood
chemical_list: D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D011163:Hydroxymethylbilane Synthase; D000623:Porphobilinogen Synthase; D015032:Zinc