endocrine and metabolic disorders
Overview of Porphyrias
Introduction
Porphyrias are rare disorders in which there are defects in the pathway of heme synthesis due to genetic or acquired deficiencies of enzymes of the heme biosynthetic pathway. These deficiencies, coupled with other factors, especially up-regulation of the first and normally rate-controlling step in the pathway, allow heme precursors to accumulate, causing toxicity. Porphyrias are defined by the specific enzyme deficiency. Two major clinical manifestations occur: neurovisceral abnormalities (the acute porphyrias) and cutaneous photosensitivity (the cutaneous porphyrias). Heme, an iron-containing pigment, is an essential cofactor of numerous hemoproteins. Virtually all cells of the human body require and synthesize heme. However, most heme (~ 85%) is synthesized in the bone marrow (by erythroblasts and reticulocytes) and is incorporated into hemoglobin. The liver is the second most active site of heme synthesis, most of which is incorporated into cytochrome P-450 enzymes. Heme synthesis requires 8 enzymes (see table). These enzymes produce and transform molecular species called porphyrinogens or porphyrins (and their precursors); accumulation of these substances causes the clinical manifestations of the porphyrias. 