Disorders of haem biosynthesis

X-Linked sideroblastic anaemia is due to a deficiency of the erythroid form of the first enzyme in the haem biosynthetic pathway, 5-aminolevulinic acid synthase. Characteristics of the disease include adult-onset anaemia, ineffective erythropoiesis with formation of ring sideroblasts, iron accumulation and pyridoxine responsiveness. Porphyrias are metabolic disorders that are due to altered activity of other enzymes of this pathway, and are associated with striking accumulations and excess excretion of haem pathway intermediates and their oxidised products. The three most common porphyrias, porphyria cutanea tarda, acute intermittent porphyria and erythropoietic protoporphyria, differ considerably from each other. Acute intermittent porphyria presents with acute neurovisceral symptoms and can be aggravated by certain drugs, hormones and nutritional changes, and is treated with intravenous haemin and carbohydrate loading. The skin is affected in the other two, although the skin manifestations and methods of diagnosis and treatment are very different.