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

Abstract

Results are presented of alpha-L-iduronidase assays in the leukocytes of normal individuals, patients with Hurler disease and heterozygous carriers. The assays were carried out using 4-methylumbelliferyl-alpha-L-iduronide and 4-trifluoromethylumbelliferyl-alpha-L-iduronide as substrates. It was shown that 4-trifluoromethylumbelliferyl-alpha-L-iduronide, along with the commonly used 4-methylumbelliferyl-alpha-L-iduronide, can serve as a specific substrate for alpha-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 alpha-L-iduronidase activity assay in fetal liver and kidney. It was found that 4-trifluoromethylumbelliferyl-alpha-L-iduronide is highly efficient for the rapid detection of alpha-L-iduronidase deficiency directly in pieces of tissues and in placenta, which is important for the prenatal diagnosis of Hurler disease.

Recent advances in the prenatal diagnosis of the mucopolysaccharidoses

“…Sensitive enzyme assays allowing discrimination of heterozygotes from homozygotes of either the wild-type or mutant genes have been described. Examples include MPS IH (Stirling et al, 1979;Tsvetkova et al, 1991), MPS IIIA (Matalon et al, 1988;Toone and Applegarth, 1988;Stone et al, 1990) and MPS IIID (Freeman and Hopwood, 1989). These assays may have applications in extended families known to be at risk for a given MPS, but in practice many laboratories lind an overlap between obligate heterozygotes and normal controls, making carrier detection within the general population unreliable.…”