@article{bfdccbfda2c646b5b664eae045308cc9,
title = "Facts and artefacts in mevalonic aciduria: development of a stable isotope dilution GCMS assay for mevalonic acid and its application to physiological fluids, tissue samples, prenatal diagnosis and carrier detection",
abstract = "A stable isotope dilution assay using D3-mevalonic acid was developed and applied to the study of mevalonic aciduria. The method also appears to be suitable for the evaluation of different therapeutic regimens in patients with hypercholesterolemia. Mevalonic acid was isolated by liquid partition chromatography and quantified as the underivatized lactone by means of ammonia chemical ionization selected ion monitoring capillary gas chromatography-mass spectrometry. In heterozygotes there was significantly greater urinary excretion of mevalonic acid, while the range of enzymatic activity of mevalonate kinase showed an overlap with that of controls. The analysis of amniotic fluids of two pregnancies at risk for mevalonic aciduria showed a 3277-fold elevation as compared to controls in the first case, diagnostic of an affected fetus, and a normal value in the second one. Mevalonic acid concentration was much increased in tissues of the affected and aborted fetus. Concentrations ranged from 840 to 1120 μmol/kg in various tissues and were as high as 1810 μmol/kg in brain. Concentrations in control fetal tissues were ≈ 1 μmol/kg.",
keywords = "Carrier detection, Cholesterol biosynthesis, Mevalonic aciduria, Prenatal diagnosis, Stable isotope dilution assay",
author = "Hoffmann, {Georg F.} and Lawrence Sweetman and Bremer, {Hans J.} and Hunneman, {Donald H.} and Josef Hy{\'a}nek and Victor Ko{\v z}ich and Willy Lehnert and Nyhan, {William L.} and Ines Speidel and Trefz, {Friedrich K.} and Gibson, {Kenneth M.}",
note = "Funding Information: The authors are indebted to the following researchersw ho contributed cell lines: Dr. I.K. Brandt, Dr. R. Berger, Dr. G.P.A. Smit, Dr. J.B.C. de Klerk, Dr. M. Duran and Dr. R.S. Wappner. We thank Dr. W. Kleijer for transporting many of the cell lines. We wish to thank Dr. Ellen Blum-Hoffmann, who carefully obtained the urines of the neonates and the nursing staff of the neonatal wards of the Medical Center of the University of California, San Diego, for their co-operation. Susanne Brendel and Claudia Seppel provided excellent assistance in maintenance of cell cultures as well as in the work up of samples for the stable isotope dilution assay. Dr. Hoffmann was supported by the Deutsche Forschungsgemeinschaft (Ho 966/2-l and Ho 966/2-2) Dr. Sweetman by a grant No. HD04608 from the National Institute of Child Health and Human Development and Dr. Gibson by Basil O{\textquoteright}Connor Award No. 5-657 and a Basic Research Grant No. 1-1171 from the March of Dimes Birth Defects Foundation. Some of the results were obtained during work for a medical thesis (I.S.).",
year = "1991",
month = may,
day = "15",
doi = "10.1016/0009-8981(91)90355-G",
language = "English (US)",
volume = "198",
pages = "209--227",
journal = "Clinica Chimica Acta",
issn = "0009-8981",
publisher = "Elsevier",
number = "3",
}