Biochemistry of porphyria.

1. The porphyrias are a group of metabolic disorders arising from defects in the haem biosynthetic pathway. Most forms are inherited as Mendelian autosomal dominants, but some types are recessive and others acquired through exposure to porphyrinogenic drugs and chemicals. There is a linked group of diseases, which are not porphyrias, but have in common alterations of haem biosynthesis. 2. The processes of haem biosynthesis are now well understood and the molecular biology of the functions and dysfunctions in the porphyrias are currently an area of intensive investigation. 3. The acute porphyrias, Acute Intermittent Porphyria, Variegate Porphyria and Hereditary Coproporphyria are of most importance since attacks of these may be life-threatening. 4. These diseases that usually present with a neurovisceral attack are characterized by excess production of the porphyrin precursors, 5-aminolaevulinate and porphobilinogen because of lowered activity of Porphobilinogen deaminase. 5. A variety of factors may precipitate these attacks including various drugs, alcohol, smoking, dieting or fasting and variations in steroid hormone levels. 6. The non-acute porphyrias are largely dermatological conditions, which present clinically as cutaneous photosensitivity. The dermatological changes are caused by the photosensitizing properties of circulating porphyrins and are accompanied by systemic effects of these porphyrins.