Gene-Environmental Interactions: Lessons from Porphyria

ABSTRACT

The porphyrias are uncommon, complex, and fascinating metabolic conditions, caused by deficiencies in the activities of the enzymes of the heme biosynthetic pathway. Two 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 greatly, and, in rare cases, may die. While congenital porphyrias are inherited, other forms of porphyria occur as acquired diseases. In addition, not all gene carriers of inherited porphyrias develop clinical disease and there is a significant interplay between the gene defect and acquired or environmental factors. The variable response of porphyrias to acquired factors may likely reflect genetic polymorphisms in drug metabolism. The lessons from acute hepatic porphyria, such as acute intermittent porphyria, are very useful in clarifying the complex nature of the clinical expression of metabolic disorders.