Hepatic protoporphyrin production in human protoporphyria. Effects of intravenous hematin and analysis of erythrocyte protoporphyrin distribution.

Human protoporphyria with atypical features suggesting increased hepatic protoporphyrin synthesis was investigated in 2 patients. Analysis of the distribution of protoporphyrin among circulating erythrocytes of increasing age indicated that the erythrocyte porphyrin burden derived predominantly from erythroid sources in case 1, and from hepatic sources in case 2. Intravenous hematin was administered to both patients to assess any negative feedback effect on protoporphyrin synthesis. Erythrocyte, fecal and plasma porphyrin levels were measured serially during basal, treatment, and follow-up periods. In case 1, a significant (P less than 0.001) drop in both fecal and plasma levels accompanied hematin, while erythrocyte levels remained unchanged. Hematin produced no appreciable changes in porphyrin concentrations in case 2. Allergic vasculitis followed hematin use in both cases. Based on data of this study and on previous data, a model for protoporphyrin transport and clearance was developed in which the variable clinical and biochemical manifestations of human protoporphyria are related to the relative contributions of erythroid and hepatic sources to the abnormal protoporphyrin pools.