Prenatal diagnosis of cystinosis by quantitative measurement of cystine in chorionic villi and cultured cells

Objective: Prenatal diagnosis of cystinosis has been available for over 30 years by the incubation of cultured amniotic cells, intact chorionic villi and cultured chorionic cells with [35S]-cystine followed by thin layer chromatography and visual inspection of autoradiographs of the chromatograms for cystine. This method has proved highly reliable but because of the short half-life of [35S]-cystine, its cost and the length of the assay procedure, an alternative method of diagnosis was investigated.

Method: Cystine was quantitatively measured in chorionic villi directly, in cultured chorionic villi and cultured amniotic cells using a cystine-binding protein from Escherichia coli.

Results: Twelve pregnancies at risk for cystinosis were monitored by both the [35S]-cystine uptake method and the new quantitative method in uncultured chorionic villi. There was no discrepancy between the results obtained with the two methods and subsequently 15 pregnancies have been monitored by the quantitative assay only--13 in chorionic villi directly, 1 in cultured chorionic villi cells and 1 in cultured amniotic cells. Grossly elevated levels of cystine were found in seven pregnancies.

Conclusion: An unequivocal diagnosis of cystinosis can be made within 24 h of sampling by the quantitative measurement of cystine in uncultured chorionic villi.