The porphyrias.

Abstract

The porphyrias are metabolic disorders in which there are excessive accumulation and excretion of porphyrins and porphyrin precursors. Each of the porphyrias has a specific enzyme defect in the pathway of heme biosynthesis that explains the pattern of biochemical abnormalities that occur. However, some patients have the enzyme defect but do not have clinical or biochemical manifestations, indicating that other factors (e.g., demand for increased heme biosynthesis) are also important in causing disease expression. The major clinical manifestations are neurologic dysfunction and photosensitivity. The precise cause of the neurologic dysfunction has not been defined, but the likely possibilities are overproduction of delta-aminolevulinic acid, which may act as a neurotoxin, or a deficiency of heme (or both). The cutaneous lesions in the porphyrias are due to the photo-sensitizing and other effects of porphyrins that are deposited in the skin or are circulating in dermal blood vessels. Therapy is directed to modify the biochemical abnormalities. Most importantly, intravenous administration of hematin is used in the treatment of acute attacks of neurologic dysfunction. Prevention remains a cornerstone in management of patients with porphyria, and those with gene defects should be counseled regarding factors that precipitate acute attacks.