Next Article in Journal
Setting up a Newborn Hearing Screening Programme in a Low-Income Country: Initial Findings from Malawi
Previous Article in Journal
A Single-Extremity Staged Approach for Critical Congenital Heart Disease Screening: Results from Tennessee
Article Menu

Export Article

Open AccessArticle
Int. J. Neonatal Screen. 2017, 3(4), 32;

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

Metabolic Laboratory, Department of Laboratory Medicine & Pathology, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
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.
Received: 23 October 2017 / Accepted: 3 November 2017 / Published: 1 December 2017
PDF [1170 KB, uploaded 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

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Neonatal Screen. EISSN 2409-515X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top