Abstract
A quantitative assay for 3-hydroxyisovaleric acid in amniotic fluid was developed using D6-3-hydroxyisovaleric acid as an internal standard. 3-Hydroxyisovaleric acid was isolated by liquid partition chromatography and the amount determined by selected ion monitoring, ammonia chemical ionization gas chromatography-mass spectrometry of the trimethylsilyl derivatives. The concentration of 3-hydroxyisovaleric acid in ten normal amniotic fluids was 4.52±1.73 µmol/l. The level was elevated eight-fold in the amniotic fluid from a pregnancy resulting in the birth of a child with biotin-responsive multiple carboxylase deficiency. The stable isotope dilution assay of 3-hydroxyisovaleric acid in amniotic fluid is a rapid, sensitive and accurate method for the prenatal diagnosis of this disorder, and may be of value in the prenatal diagnosis of other inherited disorders of leucine catabolism.
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C. Jakobs is on leave from the Department of Pediatrics, Academic Hospital of the Free University of Amsterdam, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands
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Jakobs, C., Sweetman, L., Nyhan, W.L. et al. Stable isotope dilution analysis of 3-hydroxyisovaleric acid in amniotic fluid: Contribution to the prenatal diagnosis of inherited disorders of leucine catabolism. J Inherit Metab Dis 7, 15–20 (1984). https://doi.org/10.1007/BF01805614
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DOI: https://doi.org/10.1007/BF01805614