The activities of the enzymes of haem biosynthesis in the porphyrias and during treatment of acute intermittent porphyrias

Abstract

1. 1. Development of techniques to measure the activity each of the enzymes of haem biosynthesis, excluding protoporphyrinogen oxidase, in peripheral blood has allowed an analysis of the patterns of haem biosynthesis in normal subjects and in the porphyrias. In the porphyrias, the activity of δ-aminolaevulinic acid synthase is raised and the individual patterns of porphyrin production and excretion found in each of the porphyrias, may be ascribed to specific enzyme deficiencies within the haem biosynthetic pathway. Secondary control of the biosynthetic pathway is maintained by the enzyme uroporphyrinogen 1 synthase. 2. 2. Eleven courses of intravenous haematin therapy were administered to 8 patients in acute attack of acute intermittent porphyria. Ten courses were associated with reduction of urinary excretion of porphyrins and precursors. Leucocyte δ-aminolaevulinic acid synthase activity was lowered during haematin therapy in four patients, and unequivocal clinical improvement was seen in six of the treatments. Four patients treated with intravenous laevulose showed diminished activity of ALA synthase and concentrations of porphyrin precursors combined with increases in activity of uroporphyrinogen 1 synthase.