Disorders of haem biosynthesis

Features of X-Linked sideroblastic anaemia (XLSA) due to loss of function mutations of ALAS2 include childhood-or adult-onset anaemia, ineffective erythropoiesis with formation of ring sideroblasts, iron accumulation and pyridoxine responsiveness. Porphyrias are due to altered activity of enzymes of this pathway and cause striking accumulations of pathway intermediates and their oxidised products. Erythropoietic porphyrias usually present in childhood and hepatic porphyrias during adult life. Of the three most common porphyrias, porphyria cutanea tarda (PCT) presents with chronic blistering photosensitiviry, acute intermittent porphyria (AIP) presents with acute neurovisceral symptoms that can be exacerbated by certain drugs, hormones and nutritional changes, and erythropoietic protoporphyria (EPP) with acute, nonblistering photosensitity. All porphyrias are inherited, with the exception of PCT, which is mostly due to an acquired enzyme deficiency in the liver.