Postulated deficiency of hepatic heme and repair by hematin infusions in the "inducible" hepatic porphyrias.

Abstract

There is compelling indirect evidence of hepatic heme deficiency due primarily to the respective genetic errors of the 3 inducible hepatic porphyrias, acute intermittent porphyria, porphyria variegata and hereditary coproporphyria. The induction is enhanced by exogenous inducers such as barbiturate, estrogens and other porphyrogenic chemicals and factors, including glucose deprivation. The newer knowledge of the induction of .delta.-aminolevulinic acid synthetase [.delta.-aminolevulinate synthase; succinyl-CoA:glycine C-succinyl-transferase (decarboxylating), EC 2.3.1.37] in relation to inadequate heme, and repression by heme, stimulated early trials of hematin infusions to overcome the acute relapse in the foregoing inducible porphyrias. Recently this experience was considerably expanded, 143 infusions of hematin were given in 22 cases. Studies of the effect on the serum concentrations of .delta.-aminolevulinic acid and porphobilinogen showed a highly significant decline, often to 0, especially of .delta.-aminolevulinic acid. A distinct relationship to the clinical severity of the attack was evident in the frequency and magnitude of decline of serum .delta.-aminolevulinic acid and porphobilinogen. This was regularly associated with objective clinical improvement.