Pilot study of newborn screening for six lysosomal diseases in Brazil

Francyne Kubaski; Ines Sousa; Tatiana Amorim; Danilo Pereira; Camilo Silva; Vitor Chaves; Ana Carolina Brusius-Facchin; Alice B.O. Netto; Juliano Soares; Filippo Vairo; Edina Poletto; Joe Trometer; Alexandre Souza; Enzo Ranieri; Giulia Polo; Xinying Hong; Zackary M. Herbst; Alberto Burlina; Michael H. Gelb; Roberto Giugliani

doi:10.1016/j.ymgme.2023.107654

Pilot study of newborn screening for six lysosomal diseases in Brazil

Francyne Kubaski, Ines Sousa, Tatiana Amorim, Danilo Pereira, Camilo Silva, Vitor Chaves, Ana Carolina Brusius-Facchin, Alice B.O. Netto, Juliano Soares, Filippo Vairo, Edina Poletto, Joe Trometer, Alexandre Souza, Enzo Ranieri, Giulia Polo, Xinying Hong, Zackary M. Herbst, Alberto Burlina, Michael H. Gelb, Roberto Giugliani

Medical Genetics

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Lysosomal diseases (LDs) are progressive life-threatening disorders that are usually asymptomatic at birth. Specific treatments are available for several LDs, and early intervention improves patient's outcomes. Thus, these diseases benefit from newborn screening (NBS). We have performed a pilot study for six LDs in Brazil by tandem mass spectrometry. Methods: Dried blood spot (DBS) samples of unselected newborns were analyzed by the Neo-LSD™ kit (Perkin-Elmer) by MS/MS. Samples with low enzyme activity were submitted to the evaluation of specific biomarkers by ultra-performance liquid chromatography tandem-mass spectrometry as the second-tier, and were analyzed by a next-generation sequencing (NGS) multi-gene panel as the third-tier. All tests were performed in the same DBS sample. Results: In 20,066 newborns analyzed, 15 samples showed activity of one enzyme below the cutoff. Two newborns had biochemical and molecular results compatible with Fabry disease, and five newborns had biochemical results and pathogenic variants or variants of unknown significance (VUS) in GAA. Conclusions: This study indicates that the use of enzyme assay as the first-tier test gives an acceptably low number of positive results that requires second/third tier testing. The possibility to run all tests in a DBS sample makes this protocol applicable to large-scale NBS programs.

Original language	English (US)
Article number	107654
Journal	Molecular genetics and metabolism
Volume	140
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ymgme.2023.107654
State	Published - Sep 1 2023

Keywords

Biomarkers
Enzyme analysis
Lysosomal storage diseases
Newborn screening
Tandem mass spectrometry

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Biology
Genetics
Endocrinology

Access to Document

10.1016/j.ymgme.2023.107654

Cite this

Kubaski, F., Sousa, I., Amorim, T., Pereira, D., Silva, C., Chaves, V., Brusius-Facchin, A. C., Netto, A. B. O., Soares, J., Vairo, F., Poletto, E., Trometer, J., Souza, A., Ranieri, E., Polo, G., Hong, X., Herbst, Z. M., Burlina, A., Gelb, M. H., & Giugliani, R. (2023). Pilot study of newborn screening for six lysosomal diseases in Brazil. Molecular genetics and metabolism, 140(1-2), Article 107654. https://doi.org/10.1016/j.ymgme.2023.107654

Kubaski, F, Sousa, I, Amorim, T, Pereira, D, Silva, C, Chaves, V, Brusius-Facchin, AC, Netto, ABO, Soares, J, Vairo, F, Poletto, E, Trometer, J, Souza, A, Ranieri, E, Polo, G, Hong, X, Herbst, ZM, Burlina, A, Gelb, MH & Giugliani, R 2023, 'Pilot study of newborn screening for six lysosomal diseases in Brazil', Molecular genetics and metabolism, vol. 140, no. 1-2, 107654. https://doi.org/10.1016/j.ymgme.2023.107654

@article{886fdd05095048b2af30a50fb8c52528,

title = "Pilot study of newborn screening for six lysosomal diseases in Brazil",

abstract = "Background: Lysosomal diseases (LDs) are progressive life-threatening disorders that are usually asymptomatic at birth. Specific treatments are available for several LDs, and early intervention improves patient's outcomes. Thus, these diseases benefit from newborn screening (NBS). We have performed a pilot study for six LDs in Brazil by tandem mass spectrometry. Methods: Dried blood spot (DBS) samples of unselected newborns were analyzed by the Neo-LSD{\texttrademark} kit (Perkin-Elmer) by MS/MS. Samples with low enzyme activity were submitted to the evaluation of specific biomarkers by ultra-performance liquid chromatography tandem-mass spectrometry as the second-tier, and were analyzed by a next-generation sequencing (NGS) multi-gene panel as the third-tier. All tests were performed in the same DBS sample. Results: In 20,066 newborns analyzed, 15 samples showed activity of one enzyme below the cutoff. Two newborns had biochemical and molecular results compatible with Fabry disease, and five newborns had biochemical results and pathogenic variants or variants of unknown significance (VUS) in GAA. Conclusions: This study indicates that the use of enzyme assay as the first-tier test gives an acceptably low number of positive results that requires second/third tier testing. The possibility to run all tests in a DBS sample makes this protocol applicable to large-scale NBS programs.",

keywords = "Biomarkers, Enzyme analysis, Lysosomal storage diseases, Newborn screening, Tandem mass spectrometry",

author = "Francyne Kubaski and Ines Sousa and Tatiana Amorim and Danilo Pereira and Camilo Silva and Vitor Chaves and Brusius-Facchin, {Ana Carolina} and Netto, {Alice B.O.} and Juliano Soares and Filippo Vairo and Edina Poletto and Joe Trometer and Alexandre Souza and Enzo Ranieri and Giulia Polo and Xinying Hong and Herbst, {Zackary M.} and Alberto Burlina and Gelb, {Michael H.} and Roberto Giugliani",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = sep,

day = "1",

doi = "10.1016/j.ymgme.2023.107654",

language = "English (US)",

volume = "140",

journal = "Molecular genetics and metabolism",

issn = "1096-7192",

publisher = "Academic Press Inc.",

number = "1-2",

}

TY - JOUR

T1 - Pilot study of newborn screening for six lysosomal diseases in Brazil

AU - Kubaski, Francyne

AU - Sousa, Ines

AU - Amorim, Tatiana

AU - Pereira, Danilo

AU - Silva, Camilo

AU - Chaves, Vitor

AU - Brusius-Facchin, Ana Carolina

AU - Netto, Alice B.O.

AU - Soares, Juliano

AU - Vairo, Filippo

AU - Poletto, Edina

AU - Trometer, Joe

AU - Souza, Alexandre

AU - Ranieri, Enzo

AU - Polo, Giulia

AU - Hong, Xinying

AU - Herbst, Zackary M.

AU - Burlina, Alberto

AU - Gelb, Michael H.

AU - Giugliani, Roberto

PY - 2023/9/1

Y1 - 2023/9/1

N2 - Background: Lysosomal diseases (LDs) are progressive life-threatening disorders that are usually asymptomatic at birth. Specific treatments are available for several LDs, and early intervention improves patient's outcomes. Thus, these diseases benefit from newborn screening (NBS). We have performed a pilot study for six LDs in Brazil by tandem mass spectrometry. Methods: Dried blood spot (DBS) samples of unselected newborns were analyzed by the Neo-LSD™ kit (Perkin-Elmer) by MS/MS. Samples with low enzyme activity were submitted to the evaluation of specific biomarkers by ultra-performance liquid chromatography tandem-mass spectrometry as the second-tier, and were analyzed by a next-generation sequencing (NGS) multi-gene panel as the third-tier. All tests were performed in the same DBS sample. Results: In 20,066 newborns analyzed, 15 samples showed activity of one enzyme below the cutoff. Two newborns had biochemical and molecular results compatible with Fabry disease, and five newborns had biochemical results and pathogenic variants or variants of unknown significance (VUS) in GAA. Conclusions: This study indicates that the use of enzyme assay as the first-tier test gives an acceptably low number of positive results that requires second/third tier testing. The possibility to run all tests in a DBS sample makes this protocol applicable to large-scale NBS programs.

AB - Background: Lysosomal diseases (LDs) are progressive life-threatening disorders that are usually asymptomatic at birth. Specific treatments are available for several LDs, and early intervention improves patient's outcomes. Thus, these diseases benefit from newborn screening (NBS). We have performed a pilot study for six LDs in Brazil by tandem mass spectrometry. Methods: Dried blood spot (DBS) samples of unselected newborns were analyzed by the Neo-LSD™ kit (Perkin-Elmer) by MS/MS. Samples with low enzyme activity were submitted to the evaluation of specific biomarkers by ultra-performance liquid chromatography tandem-mass spectrometry as the second-tier, and were analyzed by a next-generation sequencing (NGS) multi-gene panel as the third-tier. All tests were performed in the same DBS sample. Results: In 20,066 newborns analyzed, 15 samples showed activity of one enzyme below the cutoff. Two newborns had biochemical and molecular results compatible with Fabry disease, and five newborns had biochemical results and pathogenic variants or variants of unknown significance (VUS) in GAA. Conclusions: This study indicates that the use of enzyme assay as the first-tier test gives an acceptably low number of positive results that requires second/third tier testing. The possibility to run all tests in a DBS sample makes this protocol applicable to large-scale NBS programs.

KW - Biomarkers

KW - Enzyme analysis

KW - Lysosomal storage diseases

KW - Newborn screening

KW - Tandem mass spectrometry

UR - http://www.scopus.com/inward/record.url?scp=85166193672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85166193672&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2023.107654

DO - 10.1016/j.ymgme.2023.107654

M3 - Article

C2 - 37507255

AN - SCOPUS:85166193672

SN - 1096-7192

VL - 140

JO - Molecular genetics and metabolism

JF - Molecular genetics and metabolism

IS - 1-2

M1 - 107654

ER -

Pilot study of newborn screening for six lysosomal diseases in Brazil

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this