Development of Second-Tier Liquid Chromatography-Tandem Mass Spectrometry Analysis for Expanded Newborn Screening in Japan
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.1.1. Biological Samples
2.1.2. Chemicals
2.2. Methods
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Rinaldo, P.; Zafari, S.; Tortorelli, S.; Matern, D. Making the case for objective performance metrics in newborn screening by tandem mass spectrometry. Ment. Retard. Dev. Disabil. Res. Rev. 2006, 12, 255–261. [Google Scholar] [CrossRef]
- Wendel, U.; Langenbeck, U.; Seakin, J.W.T. Interrelation between the metabolism of L-isoleucine and L-allo-isoleucine in patients with maple syrup urine disease. Pediatr. Res. 1989, 25, 11–14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oglesbee, D.; Sanders, K.A.; Lacey, J.M.; Magera, M.J.; Casetta, B.; Strauss, K.A.; Tortorelli, S.; Rinaldo, P.; Matern, D. Second-tier test for quantification of alloisoleucine and branched-chain amino acids in dried blood spots to improve newborn screening for maple syrup urine disease (MSUD). Clin. Chem. 2008, 54, 542–549. [Google Scholar] [CrossRef] [PubMed]
- Alodaib, A.; Carpenter, K.; Wiley, V.; Sim, K.; Christodoulou, J.; Wilcken, B. An improved ultra performance liquid chromatography-tandem mass spectrometry method for the determination of alloisoleucine and branched chain amino acids in dried blood samples. Ann. Clin. Biochem. 2011, 48, 468–470. [Google Scholar] [CrossRef] [PubMed]
- Griffin, C.; Ammous, Z.; Vancea, G.H.; Grahama, B.H.; Miller, M.J. Rapid quantification of underivatized alloisoleucine and argininosuccinate using mixed-mode chromatography with tandem mass spectrometry. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2019, 1128, 121786. [Google Scholar] [CrossRef]
- Moore, T.; Le, A.; Cowan, T.M. An improved LC-MS/MS method for the detection of classic and low excretor glutaric acidemia type 1. J. Inherit. Metab. Dis. 2012, 35, 431–435. [Google Scholar] [CrossRef]
- Peng, M.; Fang, X.; Huang, Y.; Cai, Y.; Liang, C.; Lin, R.; Liu, L.J. Separation and identification of underivatized plasma acylcarnitine isomers using liquid chromatography-tandem mass spectrometry for the differential diagnosis of organic acidemias and fatty acid oxidation defects. Chromatogr. A 2013, 1319, 97–106. [Google Scholar] [CrossRef]
- Simon, G.A.; Wierenga, A. Quantitation of plasma and urine 3-hydroxyglutaric acid, after separation from 2-hydroxyglutaric acid and other compounds of similar ion transition, by liquid chromatography-tandem mass spectrometry for the confirmation of glutaric aciduria type 1. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2018, 1097–1098, 101–110. [Google Scholar] [CrossRef]
- Al-Dirbashi, O.Y.; Kölker, S.; Ng, D.; Fisher, L.; Rupar, T.; Lepage, N.; Rashed, M.S.; Santa, T.; Goodman, S.I.; Geraghty, M.T.; et al. Diagnosis of glutaric aciduria type 1 by measuring 3-hydroxyglutaric acid in dried urine spots by liquid chromatography tandem mass spectrometry. J. Inherit. Metab. Dis. 2011, 34, 173–180. [Google Scholar] [CrossRef]
- Matern, D.; Tortorelli, S.; Oglesbee, D.; Gavrilov, D.; Rinaldo, P. Reduction of the false-positive rate in newborn screening by implementation of MS/MS-based second-tier tests: The MayoClinic experience (2004–2007). J. Inherit. Metab. Dis. 2007, 30, 585–592. [Google Scholar] [CrossRef]
- Turgeon, C.T.; Magera, M.J.; Cuthbert, C.D.; Loken, P.R.; Gavrilov, D.K.; Tortorelli, S.; Raymond, K.M.; Oglesbee, D.; Rinaldo, P.; Matern, D. Determination of total homocysteine, methylmalonic acid, and 2-methylcitric acid in dried blood spots by tandem mass spectrometry. Clin. Chem. 2010, 56, 1686–1695. [Google Scholar] [CrossRef] [Green Version]
- la Marca, G.; Malvagia, S.; Pasquini, E.; Innocenti, M.; Donati, M.A.; Zammarchi, E. Rapid 2nd-tier test for measurement of 3-OH-propionic and methylmalonic acids on dried blood spots: Reducing the false-positive rate for propionylcarnitine during expanded newborn screening by liquid chromatography-tandem mass spectrometry. Clin. Chem. 2007, 53, 1364–1369. [Google Scholar] [CrossRef]
- Fu, X.; Xu, Y.K.; Chan, P.; Pattengale, P.K. Simple, fast, and simultaneous detection of plasma total homocysteine, methylmalonic acid, methionine, and 2-methylcitric acid using liquid chromatography and mass spectrometry (LC/MS/MS). JIMD Rep. 2013, 10, 69–78. [Google Scholar]
- Al-Dirbashi, O.Y.; McIntosh, N.; McRoberts, C.; Fisher, L.; Rashed, M.S.; Makhseed, N.; Geraghty, M.T.; Santa, T.; Chakraborty, P. Analysis of methylcitrate in dried blood spots by liquid chromatography-tandem mass spectrometry. JIMD Rep. 2014, 16, 65–73. [Google Scholar] [PubMed] [Green Version]
- Al-Dirbashi, O.Y.; McIntosh, N.; Chakraborty, P. Quantification of 2-methylcitric acid in dried blood spots improves newborn screening for propionic and methylmalonic acidemias. J. Med. Screen 2017, 24, 58–61. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Monostori, P.; Klinke, G.; Richter, S.; Barath, A.; Fingerhut, R.; Baumgartner, M.R.; Kolker, S.; Hoffmann, G.F.; Gramer, G.; Okun, J.G. Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders. PLoS ONE 2017, 12, e0184897. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Sun, Y.; Jiang, T. Clinical application of LC-MS/MS in the follow-up for treatment of children with methylmalonic aciduria. Adv. Ther. 2019, 36, 1304–1313. [Google Scholar] [CrossRef] [PubMed]
- Nakajima, Y.; Ito, T.; Maeda, Y.; Ichiki, S.; Sugiyama, N.; Mizuno, M.; Makino, Y.; Sugiura, T.; Kurono, Y.; Togari, H. Detection of pivaloylcarnitine in pediatric patients with hypocarnitinemia after long-term administration of pivalate-containing antibiotics. Tohoku J. Exp. Med. 2010, 221, 309–313. [Google Scholar] [CrossRef] [PubMed]
- Forni, S.; Fu, X.; Palmer, S.E.; Sweetman, L. Rapid determination of C4-acylcarnitine and C5-acylcarnitine isomers in plasma and dried blood spots by UPLC-MS/MS as a second tier test following flow-injection MS/MS acylcarnitine profile analysis. Mol. Genet. Metab 2010, 101, 25–32. [Google Scholar] [CrossRef]
- Janzen, N.; Steuerwald, U.; Sander, S.; Terhardt, M.; Peter, M.; Sander, J. UPLC-MS/MS analysis of C5-acylcarnitines in dried blood spots. Clin. Chim. Acta 2013, 421, 41–45. [Google Scholar] [CrossRef] [PubMed]
- Shigematsu, Y.; Yuasa, M.; Hata, I.; Nakajima, H.; Tajima, G.; Ishige, N.; Fukao, T.; Maeda, Y. 2-Methylacetoacetylcarnitine in blood of beta-ketothiolase deficiency and HSD10 disease. Med. Mass Spectrom. 2019, 3, 43–47. [Google Scholar]
- Maines, E.; Catesini, G.; Boenzi, S.; Mosca, A.; Candusso, M.; Strologo, L.D.; Martinelli, D.; Maiorana, A.; Liguori, A.; Olivieri, G.; et al. Plasma methylcitric acid and its correlations with other disease biomarkers: The impact in the follow up of patients with propionic and methylmalonic acidemia. J. Inherit. Metab. Dis. 2020, 43, 1173–1185. [Google Scholar] [CrossRef] [PubMed]
LC-MS/MS Method | Positive Screening Marker | Target Metabolite |
---|---|---|
1 | Leu+Ile | allo-Ile, Ile, Leu |
2-A | C3, C3/C2, Met | MMA, 3HPA, tHcy |
2-B | C3, C3/C2, Met | MMA, MCA, tHcy (derivatized) |
3 | C5-DC | GA, 3HGA |
4 | C5-OH, C5:1 | HIVA, HMGA, HMBA |
5 | C5-OH, C5:1 | short-chain acylcarnitines, acylglycines |
6 | C5 | short-chain acylcarnitines |
7 | citrulline | argininosuccinic acid |
MSUD Patient # | FI-MS/MS | LC-MS/MS | ||
---|---|---|---|---|
Acetylcarnitine | Valine | Leu+Ile | Allo-Ile | |
1 | 40.7 | 368 | 767 | 38.3 |
2 | 20.5 | 427 | 554 | 82.1 |
3 | 15.0 | 386 | 2199 | 362.6 |
4 | 17.9 | 508 | 813 | 131.0 |
false positive cases (n = 12) | 15.0–38.2 | 211–420 | 304–420 | 0.5–5.9 |
Pt # | Diagnosis | FI-MS/MS | LC-MS/MS | ||||
---|---|---|---|---|---|---|---|
C3 (μM) | C3/C2 | C3/Met | Met (μM) | MMA (μM) | tHcy (μM) | ||
1 | cblC | 10.30 | 1.10 | 1.60 | 6.40 | 59.7 | 34.8 |
2 | cblC | 15.01 | 1.10 | 0.46 | 32.5 | 44.4 | 17.0 |
3 | cobalamin deficiency 1 | 3.59 | 0.21 | 0.34 | 10.65 | 6.7 | 5.5 |
4 | cobalamin deficiency 1 | 2.14 | 0.45 | 0.35 | 6.12 | 5.5 | 11.8 |
5 | MTHFRD | 0.62 | 0.13 | 0.13 | 4.98 | 0.5 | 49.2 |
6 | MTHFRD | 0.45 | 0.05 | 0.07 | 6.63 | 0.8 | 10.6 |
7 | MTHFRD | 0.77 | 0.09 | 0.17 | 4.61 | 1.3 | 10.4 |
8 | MTHFRD | 0.53 | 0.09 | 0.08 | 6.70 | 0.8 | 28.7 |
9 | CBSD 2 | 1.00 | 0.02 | 0.00 | 911 | 0.1 | 84.7 |
upper cut-off | 3.5 | 0.25 | 0.25 | 80 | 1.0 | 5.0 | |
lower cut-off | - | - | - | 9.27 | - | - |
Analyte | Linearity (R2) | Imprecision | ||
---|---|---|---|---|
Analyte Level in DBS (μM) | CV (%) Intraassay (n = 5) | CV (%) Inter-assay (n = 5) | ||
HMGA | 0.9994 | 5.1 | 5.1 | 7.9 |
HIVA | 0.9982 | 14.7 | 7.6 | 12.2 |
HMBA | 0.9974 | 39.1 | 8.9 | 14.4 |
Diagnosis | FI-MS/MS | LC-MS/MS | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
C5-OH (µM) | Organic Acid (µM) | Acylcarnitine (µM) | Acylglycine (µM) | |||||||||
HMGA | HIVA | 3HMBA | Propionyl | HIVC | HMBC | Tiglyl | MCC 1 | Propionyl | Tiglyl | MCG 2 | ||
3-ketothiolase deficiency | 3.1 | 0.37 | 2.2 | 130.3 | 0.67 | 0.12 | 4.84 | 0.49 | <0.01 | 0.02 | 2.67 | 0.01 |
2.8 | 0.10 | 1.3 | 39.1 | 1.62 | 0.13 | 3.61 | 0.62 | <0.01 | 0.09 | 4.10 | <0.01 | |
HMGLD | 3.1 | 5.19 | 25.3 | 0.66 | 0.19 | 2.78 | 0.01 | 0.01 | <0.01 | 0.04 | 0.01 | 0.07 |
Holo-carboxylase deficiency | 2.2 | 1.04 | 624.5 | 0.44 | 1.78 | 1.44 | 0.02 | 0.03 | <0.01 | 1.49 | 0.26 | 2.10 |
3.4 | 0.19 | 187.5 | 0.53 | 4.12 | 3.35 | 0.01 | <0.01 | 0.01 | 0.73 | 0.02 | 0.91 | |
mild biotin deficiency | 1.1 | 0.04 | 5.8 | 0.11 | 0.81 | 1.09 | 0.01 | <0.01 | <0.01 | 0.01 | 0.01 | 0.04 |
3MCCD | 11.9 | 0.23 | 238.5 | 0.60 | 0.13 | 10.01 | 0.01 | <0.01 | <0.01 | 0.01 | 0.01 | 3.66 |
3.4 | 0.45 | 326.6 | 0.47 | 0.85 | 4.09 | 0.01 | <0.01 | 0.01 | 0.03 | 0.01 | 1.08 | |
Baby born to mother with 3MCCD | 6.8 | 0.11 | 14.7 | 0.39 | 0.41 | 5.10 | 0.01 | <0.01 | <0.01 | 0.02 | 0.03 | 0.43 |
3.9 | 0.24 | 11.7 | 0.55 | 0.86 | 5.69 | 0.01 | <0.01 | <0.01 | 0.02 | 0.02 | 0.01 | |
4.8 | 0.06 | 1.0 | 0.20 | 0.39 | 4.54 | 0.06 | <0.01 | <0.01 | 0.01 | 0.01 | 0.01 | |
controls (mean ± SD) | <0.5 | 0.53 ± 0.20 | 2.1 ± 0.6 | 0.60 ± 0.11 | 1.17 ± 0.45 | 0.09 ± 0.03 | <0.01 | <0.01 | <0.01 | 0.02 ± 0.01 | 0.01 ± 0.01 | <0.01 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Shigematsu, Y.; Yuasa, M.; Ishige, N.; Nakajima, H.; Tajima, G. Development of Second-Tier Liquid Chromatography-Tandem Mass Spectrometry Analysis for Expanded Newborn Screening in Japan. Int. J. Neonatal Screen. 2021, 7, 44. https://doi.org/10.3390/ijns7030044
Shigematsu Y, Yuasa M, Ishige N, Nakajima H, Tajima G. Development of Second-Tier Liquid Chromatography-Tandem Mass Spectrometry Analysis for Expanded Newborn Screening in Japan. International Journal of Neonatal Screening. 2021; 7(3):44. https://doi.org/10.3390/ijns7030044
Chicago/Turabian StyleShigematsu, Yosuke, Miori Yuasa, Nobuyuki Ishige, Hideki Nakajima, and Go Tajima. 2021. "Development of Second-Tier Liquid Chromatography-Tandem Mass Spectrometry Analysis for Expanded Newborn Screening in Japan" International Journal of Neonatal Screening 7, no. 3: 44. https://doi.org/10.3390/ijns7030044