BIOCHEMICAL DISCRIMINATION OF HURLER AND SCHEIE SYNDROMES

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-[1-3H]mannitol 6-sulphate although at considerably reduced rates compared with normal controls. 2. The V(max.) 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.