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A Rapid Screening Method for the Measurement of Neonatal Total Homocysteine in Dried Blood Spots by Liquid Chromatography-Tandem Mass Spectrometry

1
Metabolic Laboratory, Department of Laboratory Medicine & Pathology, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
2
Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
Current address: Reference Laboratory for Neonatal Screening, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
Int. J. Neonatal Screen. 2017, 3(4), 32; https://doi.org/10.3390/ijns3040032
Received: 23 October 2017 / Accepted: 3 November 2017 / Published: 1 December 2017
Homocystinuria (HCU) due to cystathionine-β-synthase deficiency is generally regarded as a rare disease, but within the Qatari population has an incidence of 1 in 1800 live births. Most newborn screening methods for HCU using dried blood spots (DBS) rely on the detection of an elevated methionine level or a rapid screen for total homocysteine (tHCY). However, screening based on methionine levels alone lacks specificity and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for tHCY exhibit variable results with high false positive rates. This report describes a LC-MS/MS method for detection of tHCY on DBS, with improved specificity. tHCY was extracted from DBS with a solution containing dithiothreitol and subsequently butylated with hydrochloric acid in n-butanol. The butyl esters were separated by liquid chromatography on a reverse-phase column and the homocysteine (HCY), detected by tandem mass spectrometry. The butyl ester of HCY eluted at 1.8 min. Total analysis time was 6.1 min per sample, including column flush and equilibration. This method allows for the quantification of tHCY over a linear range from 0.3 to 200 µM. Intraassay and interassay imprecision and recoveries were acceptable. Good concordance was observed with another LC-MS/MS method. Application of this method improves specificity and reduces false positive rates in screening for HCU. View Full-Text
Keywords: homocysteine; homocystinuria; cystathionine-β-synthase deficiency; newborn screening homocysteine; homocystinuria; cystathionine-β-synthase deficiency; newborn screening
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Maase, R.; Skrinska, V.; Younes, N.; Hassan, L.; Mitri, R.; Matern, D.; Rinaldo, P.; Turgeon, C. A Rapid Screening Method for the Measurement of Neonatal Total Homocysteine in Dried Blood Spots by Liquid Chromatography-Tandem Mass Spectrometry. Int. J. Neonatal Screen. 2017, 3, 32.

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