Use of 4-trifluoromethylumbelliferyl-α-l-iduronide as a new substrate for detection of α-l-iduronidase deficiency in human tissues and for rapid prenatal diagnosis of Hurler disease

Summary

Results are presented of α-l-iduronidase assays in the leukocytes of normal individuals, patients with Hurler disease and heterozygous carriers. The assays were carried out using 4-methylumbelliferyl-α-l-iduronide and 4-trifluoromethylumbelliferyl-α-l-iduronide as substrates. It was shown that 4-trifluoromethylumbelliferyl-α-l-iduronide, along with the commonly used 4-methylumbelliferyl-α-l-iduronide, can serve as a specific substrate for α-l-iduronidase and is therefore suitable for demonstrating the enzyme deficiency in patients with Hurler disease, as well as the decrease of enzyme activity in heterozygous disease carriers. Using the two substrates a prenatal diagnosis of Hurler disease in a fetus was made on the basis of the lack of enzyme activity in amniotic fluid cell cultures. The diagnosis was confirmed by the results of α-l-iduronidase activity assay in fetal liver and kidney. It was found that 4-trifluoromethylumbelliferyl-α-l-iduronide is highly efficient for the rapid detection of α-l-iduronidase deficiency directly in pieces of tissues and in placenta, which is important for the prenatal diagnosis of Hurler disease.