Abstract
ABSTRACT: A stable isotope dilution method was developed to measure accurately small amounts of isovalerylglycine in amniotic fluid and urine for the prenatal diagnosis of isovaleric acidemia. [4,4,4-D3]Isovalerylglycine was synthesized and used as an internal standard. Samples were extracted, methylated, and analyzed by chemical ionization gas chromatography-mass spectrometry operated in the selected ion monitoring mode. This method is very sensitive (lower limit ~5 ng/ml), linear over three orders of magnitude above 10 ng/ml up to at least 10 µg/ml and reproducible. No isovalerylglycine was detected at all in amniotic fluids from eleven normal pregnant women with an exception of a single case which contained 6 ng/ml. Amniotic fluids from five pregnancies at risk were analyzed. Two of these samples had isovalerylglycine concentrations of 957 and 556 ng/ml. Three others contained 18, 18, and 17 ng/ ml of isovalerylglycine. Postpartum diagnostic tests and/or in vitro assay of isovaleryl-CoA dehydrogenase of [1-14C] isovaleric acid oxidation using amniocytes confirmed that the first two fetuses were affected by isovaleric acidemia, whereas the latter three were unaffected. The method described in this report provides a highly accurate and reliable technique for the prenatal diagnosis of isovaleric acidemia.
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Hine, D., Hack, A., Goodman, S. et al. Stable Isotope Dilution Analysis of Isovalerylglycine in Amniotic Fluid and Urine and Its Application for the Prenatal Diagnosis of Isovaleric Acidemia. Pediatr Res 20, 222–226 (1986). https://doi.org/10.1203/00006450-198603000-00005
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DOI: https://doi.org/10.1203/00006450-198603000-00005
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