Biochemical Discrimination of Hurler and Scheie Syndromes

Abstract

1. Homogenates of cultured skin fibroblasts derived from patients with α-l-iduronidase-deficiency disorders (Hurler and Scheie syndromes) were capable of hydrolysing iduronosyl anhydro-[l-3H]mannitol 6-sulphate although at considerably reduced rates compared with normal controls. 2. The Vmax. values of α-l-iduronidase from patients with Hurler or Scheie syndromes and from normal controls were 11, 12 and 833 pmol min−1 mg−1 of protein respectively; the corresponding apparent Km values were 656, 50 and 53 μmol/l respectively. The α-l-iduronidases from normal and Scheie fibroblast homogenates were shown to exhibit pH optima at 3·6 and 4·1 and were competitively inhibited by both chloride and sulphate ions: Hurler α-l-iduronidase activity exhibited one pH optimum at 3·8 and was also inhibited by chloride and to a lesser extent by sulphate ions. 3. The thermal stability of Hurler, Scheie and normal α-l-iduronidase activities at 55°C gave half-lives of approximately 1·0, 2·5 and 1·0 h respectively. 4. These biochemical findings clearly demonstrate enzyme differences for these two clinically distinct phenotypes and provide biochemical evidence that the Hurler and Scheie syndromes result from different allelic mutations.