Association of amino levulinate dehydratase levels and ferrochelatase inhibition in childhood lead exposure.

The basis for the clinical variation in response to lead exposure in children is not well understood. We studied selected children from a large lead screening program in whom elevation of red cell protoporphyrin concentration (a measure of inhibition of the enzyme ferrochelatase) was markedly above or below average for a given blood lead level. We then measured the activity of the enzyme amino levulinate dehydratase in 306 of these children, and found that ALA-d activity was lower in children with higher protoporphyrin elevation, independent of the effects of lead. This observation, coupled with reports in the literature of families with ALA-d deficiencies and elevated red cell protoporphyrin values, makes likely a genetic basis for some of the variation in susceptibility to lead. The mechanism by which the two effects are associated remains unknown.