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

Mol Genet Metab. 2023 Sep-Oct;140(1-2):107654. doi: 10.1016/j.ymgme.2023.107654. Epub 2023 Jul 13.

Authors

Francyne Kubaski¹, Ines Sousa², Tatiana Amorim³, Danilo Pereira⁴, Camilo Silva⁵, Vitor Chaves⁶, Ana Carolina Brusius-Facchin⁷, Alice B O Netto⁸, Juliano Soares⁹, Filippo Vairo¹⁰, Edina Poletto¹¹, Joe Trometer¹², Alexandre Souza¹³, Enzo Ranieri¹⁴, Giulia Polo¹⁵, Xinying Hong¹⁶, Zackary M Herbst¹⁷, Alberto Burlina¹⁸, Michael H Gelb¹⁹, Roberto Giugliani²⁰

Affiliations

¹ Greenwood Genetic Center, Biochemical Genetics Laboratory, Greenwood, USA; BioDiscovery Laboratory, HCPA, Porto Alegre, Brazil; Medical Genetics Service, HCPA, Porto Alegre, Brazil; PPGBM, UFRGS, Porto Alegre, Brazil. Electronic address: fkubaski@ggc.org.
² APAE Salvador, Salvador, Brazil. Electronic address: ines.sousa@apaesalvador.org.br.
³ APAE Salvador, Salvador, Brazil; Colegiado de Medicina, Universidade do Estado da Bahia, Salvador, Brazil. Electronic address: tatiana.amorim@apaesalvador.org.br.
⁴ Innovatox, Sao Paulo, Brazil. Electronic address: danilopereira@innovatox.com.br.
⁵ Waters technologies do Brazil, Sao Paulo, Brazil. Electronic address: Camilo_Silva@waters.com.
⁶ Waters technologies do Brazil, Sao Paulo, Brazil. Electronic address: vitor_chaves@waters.com.
⁷ BioDiscovery Laboratory, HCPA, Porto Alegre, Brazil; Medical Genetics Service, HCPA, Porto Alegre, Brazil. Electronic address: afacchin@hcpa.edu.br.
⁸ BioDiscovery Laboratory, HCPA, Porto Alegre, Brazil; PPGBM, UFRGS, Porto Alegre, Brazil. Electronic address: alicenetto@hcpa.edu.br.
⁹ BioDiscovery Laboratory, HCPA, Porto Alegre, Brazil.
¹⁰ Department of Clinical Genomics, Center for Individualized Medicine, Mayo Clinic, Rochester, USA. Electronic address: vairo.filippo@mayo.edu.
¹¹ Medical Genetics Service, HCPA, Porto Alegre, Brazil; PPGBM, UFRGS, Porto Alegre, Brazil.
¹² Perkin Elmer, Waltham, USA. Electronic address: joe.trometer@perkinelmer.com.
¹³ Perkin Elmer, Sao Paulo, Brazil. Electronic address: alexandre.souza@perkinelmer.com.
¹⁴ Women's and Children Hospital, Adelaide, Australia. Electronic address: Enzo.Ranieri@sa.gov.au.
¹⁵ Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening, Department of Women and Children's Health, University Hospital of Padova, Padova, Italy.
¹⁶ Department of Chemistry, University of Washington, Seattle, USA; Department of Pathology and Laboratory of Medicine, Children's Hospital of Philadelphia, Philadelphia, USA. Electronic address: hongx@chop.edu.
¹⁷ Department of Chemistry, University of Washington, Seattle, USA. Electronic address: zherbst@uw.edu.
¹⁸ Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening, Department of Women and Children's Health, University Hospital of Padova, Padova, Italy. Electronic address: alberto.burlina@unipd.it.
¹⁹ Department of Chemistry, University of Washington, Seattle, USA. Electronic address: gelb@uw.edu.
²⁰ BioDiscovery Laboratory, HCPA, Porto Alegre, Brazil; Medical Genetics Service, HCPA, Porto Alegre, Brazil; PPGBM, UFRGS, Porto Alegre, Brazil; DASA, Sao Paulo, Brazil; Casa dos Raros, Porto Alegre, Brazil. Electronic address: rgiugliani@hcpa.edu.br.

PMID: 37507255
DOI: 10.1016/j.ymgme.2023.107654

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.

Keywords: Biomarkers; Enzyme analysis; Lysosomal storage diseases; Newborn screening; Tandem mass spectrometry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brazil / epidemiology
Fabry Disease* / diagnosis
Humans
Infant, Newborn
Neonatal Screening* / methods
Pilot Projects
Tandem Mass Spectrometry / methods