Oral charcoal therapy of congenital erythropoietic porphyria.

Abstract

Günther's disease, or congenital erythropoietic porphyria, is a rare autosomal recessive disorder of heme biosynthesis characteristically associated with diminished uroporphyrinogen III cosynthetase activity. Disfiguring photomutilation starts in childhood. Avoidance of sunlight has been the only sure way to prevent or retard photosensitivity. The treatments that have been tried have had limited success. A partial benefit after splenectomy has been reported, but there is little evidence of specific, long-term improvement. Haining and colleagues first reported suppression of bone marrow release of porphyrins by induced polycythemia, supporting the notion that disease activity can be modulated by diminishing porphyrin overproduction at the source (i.e., the bone marrow). Recently, Piomelli et al. reported complete suppression of symptoms in a 10-year-old child treated from birth with transfusion therapy and with splenectomy. Another approach is the use of orally administered sorbents such as charcoal and cholestyramine, which bind porphyrins in vitro, to retard enteral absorption of endogenous porphyrins excreted into the gut lumen. Cholestyramine has been reported to reduce photocutaneous sensitivity in porphyria cutanea tarda and to reverse the hepatic lesion in protoporphyria. In this study, we compared different treatments for progressive photomutilation in a patient with congenital erythropoietic porphyria. The effects of short-term hypertransfusion were evaluated, as was the efficacy of long-term transfusion therapy over a two-year period. To test the potential usefulness of porphyrin-binding drugs, we estimated the enteral absorption of endogenous porphyrins in the proximal small bowel and monitored the effects on tissue and excreted porphyrins of short-term oral challenges with activated charcoal (ActaChar) and with cholestyramine. Charcoal therapy was more effective than cholestyramine and therefore was subsequently administered for a long period. The data collected allow comparison of long-term charcoal therapy and long-term blood-transfusion therapy. Treatment with charcoal for nine months lowered porphyrin levels in plasma and skin and resulted in a complete clinical remission during therapy. (A preliminary report on part of this work has appeared elsewhere).