The Porphyrias

A gallery of maladies result when the synthesis of heme goes awry. They are the porphyrias, named for heme’s basic porphyrin chemical structure. All these conditions are purposeless, nasty, and fortunately rare. When heme is assembled—step by step in eight stages—a different enzyme is involved in completing each. If an enzyme cannot complete its step, heme synthesis is derailed: the amount of heme produced is reduced, and heme precursors behind the blocked enzyme accumulate (in either liver cells or red cells). Different precursors attack different parts of the body—variably the nervous system, skin (in combination with sunlight), red cells, or liver cells. Most patients fit neatly into one of several syndromes. Rare as they are, these conditions deserve greater physician and public awareness. Treatments are discussed. The porphyrias are excellent candidates for promising gene therapies.