ReviewArtiele Gene - EnvironmentalInteractions : Lessons from Porphyria Shigeru SASSA

The porphyrias are uncommon, compSex, and fascinating metabolic conditions, caused by deficiencies in the activities ofthe enzymes ofthe heme biosynthetic pathway. ISvo cardinal symptoms of the porphyrias are cutaneous photosensitivity and neurologic disturbances. Molecular analysis of gene defects has shown that there are multiple and heterogeneous mutations in each porphyria. Patients with symptomatic porphyria can suffer greatlM and, in rare eases, may die. Whlle congenital porphyrias are inherited, other forms of porphyria occur as acquired diseases. In addition, not all gene carriers of inherited porphyrias deyelop clinical disease and there is a significant interplay between the gene defect and acquired or environmental facters. The yariable response ofporphyrias to acquired factors may likely refiect genetic polymorphisms in drug metabolism. The lessons from acute hepatic porphyria, such as acute intermittent perphyria, are very usefu1 in clarifying the complex nature ofthe elinical expression of metabolic disorders.