Acute lead poisoning in inherited porphobilinogen synthase (?-aminolevulinic acid dehydrase) deficiency

Abstract

The second enzyme of the porphyrin and heme synthesis pathway, porphobilinogen synthase (EC 4.2.1.24), can be lowered due to a hereditary defect or toxic damage. Lead is the most common cause for a toxically lowered activity. We report on a 48-year-old patient with an acute abdominal syndrome, anemia and a grave toxic disorder of porphyrin metabolism which was diagnosed as acute lead intoxication. Although the hematologic findings and porphyrins in the blood, as well as porphyrin precursors and porphyrin excretion in the urine, returned to normal within five months after exacerbation of the acute symptoms the activity of porphobilinogen synthase showed only 50% physiologic activity of healthy subjects six years after the acute syndrome with complete normalization of prophyrin metabolites and lead levels in blood and urine. The influence of alcohol was excluded. Enzyme activation by zinc and reactivation by dithiothreitol lies within the normal range and thus contradicts an increased body burden of lead. In connection with findings of a familiar porphobilinogen synthase defect we are most likely dealing with a hereditarily determined enzyme deficiency in this patient which sensitizes him to a lead intoxication.

Porphobilinogen-synthase (?-aminolevulinic acid dehydratase) deficiency in bone marrow cells of two patients with porphobilinogen-synthase defect acute porphyria

“…The high urinary ALA and coproporphyrin excretion in PBG-S defect porphyria is probably of hepatic origin, in analogy to the three known acute hepatic porphyfias [8] and acute lead poisoning [11,13]. The metabolite profile in acute hepatic porphyrias, including lead poisoning, is a synergistic resultant of the consequence of the enzyme defect and its compensation, that is to say, its counterregulation.…”

“…The enzyme was reactivated by dithiothreitol [19] and activated by zinc ions [11]. Protoporphyrin was assayed by analytical thin-layer chromatography in combination with recording spectrophotometry [7] and characterized by spectrophotofluorometric differentiation between free and zinc-bound protoporphyrin [17].…”

Environmental Chemical Exposures and Disturbances of Heme Synthesis

“…A later study, however, reported chloracne but no PCT attributable to TCDDs among Seveso children and adolescen (123,124). In two studies of Missouri communities where TCDD-contaminated waste oil had been sprayed for dust control over several years, there were no cases of PCT, but one study found significantly higher mean uroporphyrin levels in urine and higher prevalence of elevated urine uroporphyrin values (> 13 pg/g creatinine (cre) in 16%, vs 7% controls) among 154 residents of a contaminated mobile home park compared to matched control subjects (125,126). in Yusho, Japan, about 10 years after the event, found no differences in urine porphyrins compared to those of controls and identified PCT in 1 person whose history was complicated by alcohol use (133,134).…”

Influence of the common human delta-aminolevulinate dehydratase polymorphism on lead body burden.

“…Furthermore, affected individuals with the recessive ALAD-deficient porphyria manifest chronic neurologic manifestations (20)(21)(22). Finally, asymptomatic heterozygotes for the latter porphyria develop acute lead poisoning when exposed to low levels of lead (23,24).…”