Stable-isotope dilution gas chromatography-mass spectrometric measurement of 3-hydroxyglutaric acid, glutaric acid and related metabolites in body fluids of patients with glutaric aciduria type 1 found in newborn screening.
We developed a simple and sensitive stable-isotope dilution method for the quantification of 3-hydroxyglutaric acid (3HGA) and glutaric acid (GA) in body fluids. In our method, tert-butyldimethylsilyl (tBDMS) derivatives of 3HGA and GA were measured with a conventional electron-impact ionization (EI) mode in gas chromatography-mass spectrometry (GC-MS). The control values for 3HGA in nmol/ml were 0.15+/-0.08 (serum; n=10) and 0.07+/-0.03 (CSF; n=10). In addition, glutarylcarnitine and free carnitine were quantified by electrospray tandem mass spectrometry. Using these methods, we monitored 3HGA, GA, and glutarylcarnitine in the body fluids of three patients with glutaric aciduria type 1 found during newborn screening. None of the patients had experienced neurological strokes, which are possibly caused by the accumulation of 3HGA, at 15-24 months of age under a disease-specific treatment, including carnitine supplementation. Our data showed that 3HGA levels were relatively high in some serum samples with lower glutarylcarnitine and carnitine levels, suggesting that carnitine supplementation may play a role in preventing the accumulation of 3HGA in patients with this disease.
Shigematsu
Yosuke
Y
Department of Health Science, Faculty of Medical Sciences, University of Fukui, Matsuoka-cho, Fukui 910-1193, Japan. yosuke@fmsrsa.fukui-med.ac.jp
Hata
Ikue
I
Tanaka
Yukie
Y
Tajima
Go
G
Sakura
Nobuo
N
Naito
Etsuo
E
Yorifuji
Toru
T
D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000378:metabolism; D003903:Deuterium / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D005977:Glutarates / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
C108959:3-hydroxyglutaric acid; D005977:Glutarates; D003903:Deuterium; C035736:glutaric acid