TY - JOUR
T1 - Isotope dilution analysis of methylcitric acid in amniotic fluid for the prenatal diagnosis of propionic and methylmalonic acidemia
AU - Naylor, Gordon
AU - Sweetman, Lawrence
AU - L. Nyhan, William
AU - Hornbeck, Cecil
AU - Griffiths, John
AU - Mörch, Lars
AU - Brandänge, Svante
N1 - Funding Information:
This work was supported in part by US Public Health Services Grant No. HD-04608 from the National Institute of Child Health and Human Development and Grant No. GM-17702 from the National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD, U.S.A.
PY - 1980
Y1 - 1980
N2 - A stable isotope dilution assay for methylcitric acid in amniotic fluid was developed to provide rapid prenatal diagnosis of the inherited disorders propionic acidemia and methylmalonic acidemia. The method utilizes two 2H3-labeled diastereoisomers of methylcitric acid as internal standards, isolation by liquid partition chromatography and quantitation of the trimethyl esters by chemical ionization selected ion monitoring gas chromatography-mass spectrometry. Methylcitric acid at a concentration of 0.38 ± 0.10 μmol/1 was detected in normal amniotic fluid. Highly elevated levels of 7.87 and 9.16 μmol were found in the fluids surrounding fetuses affected with propionic acidemia and levels of 1.79, 2.72 and 12.27 μmol were found for fetuses with methylmalonic acidemia. Methylcitric acid was not elevated in the amniotic fluid of a fetus heterozygous for propionic acidemia. In the five pregnancies at risk for propionic acidemia, and three pregnancies at risk for methylmalonic acidemia, the levels of methylcitric acid in amniotic fluid gave the diagnosis in all cases. Measurement of methylcitric acid in amniotic fluid therefore provides a rapid and reliable method for the prenatal diagnosis of these genetic disorders.
AB - A stable isotope dilution assay for methylcitric acid in amniotic fluid was developed to provide rapid prenatal diagnosis of the inherited disorders propionic acidemia and methylmalonic acidemia. The method utilizes two 2H3-labeled diastereoisomers of methylcitric acid as internal standards, isolation by liquid partition chromatography and quantitation of the trimethyl esters by chemical ionization selected ion monitoring gas chromatography-mass spectrometry. Methylcitric acid at a concentration of 0.38 ± 0.10 μmol/1 was detected in normal amniotic fluid. Highly elevated levels of 7.87 and 9.16 μmol were found in the fluids surrounding fetuses affected with propionic acidemia and levels of 1.79, 2.72 and 12.27 μmol were found for fetuses with methylmalonic acidemia. Methylcitric acid was not elevated in the amniotic fluid of a fetus heterozygous for propionic acidemia. In the five pregnancies at risk for propionic acidemia, and three pregnancies at risk for methylmalonic acidemia, the levels of methylcitric acid in amniotic fluid gave the diagnosis in all cases. Measurement of methylcitric acid in amniotic fluid therefore provides a rapid and reliable method for the prenatal diagnosis of these genetic disorders.
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U2 - 10.1016/0009-8981(80)90445-3
DO - 10.1016/0009-8981(80)90445-3
M3 - Article
C2 - 7002368
AN - SCOPUS:0018955772
SN - 0009-8981
VL - 107
SP - 175
EP - 183
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 3
ER -