Investigating the suitability of high-resolution mass spectrometry for newborn screening
Standard
Investigating the suitability of high-resolution mass spectrometry for newborn screening : identification of hemoglobinopathies and β-thalassemias in dried blood spots. / Wiesinger, Thomas; Mechtler, Thomas; Schwarz, Markus; Xie, Xiaolei; Grosse, Regine; Nieves Cobos, Paulina; Kasper, David; Lukacs, Zoltan.
In: CLIN CHEM LAB MED, Vol. 58, No. 5, 28.04.2020, p. 810-816.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Investigating the suitability of high-resolution mass spectrometry for newborn screening
T2 - identification of hemoglobinopathies and β-thalassemias in dried blood spots
AU - Wiesinger, Thomas
AU - Mechtler, Thomas
AU - Schwarz, Markus
AU - Xie, Xiaolei
AU - Grosse, Regine
AU - Nieves Cobos, Paulina
AU - Kasper, David
AU - Lukacs, Zoltan
PY - 2020/4/28
Y1 - 2020/4/28
N2 - A fast and reliable method for the determination of hemoglobinopathies and thalassemias by high-resolution accurate mass spectrometry (HRAM/MS) is presented. The established method was verified in a prospective clinical study (HRAM/MS vs. high-pressure liquid chromatography [HPLC]) of 5335 de-identified newborn samples from the Hamburg area. The analytical method is based on a dual strategy using intact protein ratios for thalassemias and tryptic digest fragments for the diagnosis of hemoglobinopathies. Due to the minimal sample preparation and the use of flow injection, the assay can be considered as a high-throughput screening approach for newborn screening programs (2 min/sample). Using a simple dried blood spot (DBS) extraction (tryptic digest buffer), the following results were obtained: (1) a carrier incidence of 1:100 newborns (35 FAS, nine FAC, eight FAD and two FAE), and (2) no homozygous affected patient was detected. Using the HRAM/MS protocol, an unknown Hb mutation was identified and confirmed by genetic testing. In addition to greater specificity toward rare mutations and β-thalassemia, the low price/sample (1-2€) as well as an automated data processing represent the major benefits of the described HRAM/MS method.
AB - A fast and reliable method for the determination of hemoglobinopathies and thalassemias by high-resolution accurate mass spectrometry (HRAM/MS) is presented. The established method was verified in a prospective clinical study (HRAM/MS vs. high-pressure liquid chromatography [HPLC]) of 5335 de-identified newborn samples from the Hamburg area. The analytical method is based on a dual strategy using intact protein ratios for thalassemias and tryptic digest fragments for the diagnosis of hemoglobinopathies. Due to the minimal sample preparation and the use of flow injection, the assay can be considered as a high-throughput screening approach for newborn screening programs (2 min/sample). Using a simple dried blood spot (DBS) extraction (tryptic digest buffer), the following results were obtained: (1) a carrier incidence of 1:100 newborns (35 FAS, nine FAC, eight FAD and two FAE), and (2) no homozygous affected patient was detected. Using the HRAM/MS protocol, an unknown Hb mutation was identified and confirmed by genetic testing. In addition to greater specificity toward rare mutations and β-thalassemia, the low price/sample (1-2€) as well as an automated data processing represent the major benefits of the described HRAM/MS method.
U2 - 10.1515/cclm-2019-0832
DO - 10.1515/cclm-2019-0832
M3 - SCORING: Journal article
C2 - 32031968
VL - 58
SP - 810
EP - 816
JO - CLIN CHEM LAB MED
JF - CLIN CHEM LAB MED
SN - 1434-6621
IS - 5
ER -
