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Stable isotope dilution analysis of 3‐hydroxyisovaleric acid in amniotic fluid: Contribution to the prenatal diagnosis of inherited disorders of leucine catabolism
Author(s) -
Jakobs C.,
Sweetman L.,
Nyhan W. L.,
Packman S.
Publication year - 1984
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01805614
Subject(s) - amniotic fluid , isotope dilution , catabolism , fetoscopy , amniocentesis , chemistry , peroxisomal disorder , leucine , glutaric acid , fetus , biochemistry , medicine , chromatography , prenatal diagnosis , endocrinology , pregnancy , metabolism , amino acid , mass spectrometry , biology , genetics , peroxisome , gene
A quantitative assay for 3‐hydroxyisovaleric acid in amniotic fluid was developed using D 6 ‐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.