In inherited porphyrias, lead intoxication is a toxogenetic disorder.
1. delta-Aminolevulinic acid dehydratase (ALA-D), blood lead and several enzymes and metabolites of the heme biosynthetic pathway were measured in a number of symptomatic porphyric patients, 22 with acute intermittent porphyria, three with hereditary hepatic coproporphyria, 10 with hereditary porphyria cutanea tarda, two with erythropoietic protoporphyria and two with congenital erythropoietic porphyria and in 84 lead intoxicated persons. 2. In the 39 individuals suffering from the inherited porphyrias and in 32 lead poisoned patients with a 30-50% reduced deaminase, blood lead content was not sufficiently increased (average 28 micrograms%) to account for the greatly decreased activity of ALA-D (average 36% of controls). 3. After a relatively trifling lead exposure they developed the signs of acute lead intoxication. 4. A second group of lead intoxicated patients showing low ALA-D activity and corresponding high concentration of lead in blood, exhibited no other physiologic deviation in the enzymes and metabolites of porphyrin biosynthesis. 5. Individuals with inherited porphyrias are ultrasensitive to low level lead exposure and that lead would also act as a triggering factor. In these patients, lead intoxication can be considered a toxogenetic disorder. 6. An inversely linear correlation between ALA-D activity and blood lead content was obtained for both groups of lead intoxicated patients, however, a different constant (k) for each was obtained, which we have taken as a measure of lead toxogeneticity: k = 10 +/- 1 for lead intoxicated individuals with otherwise normal heme metabolism and k = 5 +/- 0.5 for lead intoxicated symptomatic porphyric patients. 7. Determination of erythrocytic ALA-D, besides blood lead, will be a valuable indicator for preventive medical care for these patients, when they are expected to be exposed to lead either environmentally or in their professional life.
D006418:Heme / Q000096:biosynthesis; D006801:Humans; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000097:blood / Q000150:complications* / Q000235:genetics; D000623:Porphobilinogen Synthase / Q000097:blood / Q000172:deficiency*; D011164:Porphyrias / Q000097:blood / Q000150:complications / Q000235:genetics*
D007854:Lead; D006418:Heme; D000623:Porphobilinogen Synthase