title: A nonpathologic allele (IW) for low alpha-L-iduronidase enzyme activity vis-a-vis prenatal diagnosis of Hurler syndrome.
abstract: We identified a phenotypically normal obligate heterozygote for Hurler syndrome with exceedingly low levels of alpha-L-iduronidase enzyme activity. Subsequent investigation determined that low alpha-L-iduronidase activity was systemic, also characteristic of the subject's leukocytes and cultured skin fibroblasts. Residual alpha-L-iduronidase activity of cultured fibroblasts was found to have reduced catalytic activity (Vmax) against the 4-methylumbelliferone substrate, but normal substrate affinity (KM). Additional studies further characterized the residual enzyme activity in this woman who is an apparent compound heterozygote for Hurler syndrome, and for an allele with low alpha-L-iduronidase activity lacking pathologic manifestation. Such low activity "pseudodeficiency" alleles will complicate attempts at prenatal diagnosis of Hurler syndrome and related disorders in rare families.
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D005260:Female; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006801:Humans; D007068:Iduronidase / Q000378:metabolism*; D008297:Male; D008059:Mucopolysaccharidosis I / Q000201:enzymology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D006026:Glycoside Hydrolases; D007068:Iduronidase