Treatment of the porphyrias: Mechanisms of action

Abstract

The porphyrias are diseases that result from inherited or acquired abnormalities of porphyrin-heme synthesis in the liver and the bone marrow. Only the hepatic porphyrias are known to be aggravated by exposure to a variety of exogenous drugs and chemicals. Simple avoidance of these agents will reduce the risk of developing hepatic porphyria and may lead to clinical improvement in patients with active disease. Some types of therapy of the hepatic porphyrias are effective because of their ability to modulate the activity of δ-aminolevulinic acid synthetase, the rate-limiting enzyme for heme synthesis. Most of the porphyrias are associated with cutaneous photosensitivity, the treatment of which centers about either reducing the excessive production of porphyrins or of inhibiting the photobiological response to these photosensitizing chemicals in the skin.