Post- and pre-natal assessment of alpha-L-iduronidase deficiency with a radiolabelled natural substrate.

1. a-L-Iduronidase activity was assayed by incubation of iduronosyl anhydro[ l-3H]mannitol 6-sulphate with homogenates of cultured skin fibroblasts, amniotic cells and leucocytes derived from normal individuals, patients affected with GLiduronidase deficiency disorder (mucopolysaccharidosis type I: Hurler, Scheie and Hurler-Scheie compound) and parents of such patients. 2. The assay for cc-L-iduronidase, described for use with these cell types, clearly distinguished affected homozygotes from heterozygotes and normal controls. 3. The mean specific activity of a-L-iduronidase in homogenates prepared from cultured skin fibroblasts and leucocytes from more than seven obligate heterozygotes for mucopolysaccharidosis type I was found to be about one-half of the mean of more than 40 normal controls. A number of heterozygotes had a-L-iduronidase activity that identified them as carriers; others had values clearly within the normal range. Thus heterozygote detection of mucopolysaccharidosis type I is not certain. 4. With iduronosyl anhydr~[l-~Hlmannitol 6sulphate used as substrate, cell types from five pregnancies at risk for a-L-iduronidase deficiency were examined; each foetus was predicted to be unaffected. For one foetus it was not possible from measurements of total enzyme activity alone to distinguish between the heterozygous carrier state and