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Pilot study of newborn screening for six lysosomal diseases in Brazil
Francyne Kubaski1, Ines Sousa2, Tatiana Amorim3
1Greenwood 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.
Insights
Newborn screening for lysosomal diseases (LDs) in Brazil using tandem mass spectrometry identified two cases of Fabry disease and five potential cases of Pompe disease. This pilot study demonstrates a viable protocol for large-scale newborn screening programs.
Area of Science:
- Biochemistry
- Genetics
- Public Health
Background:
- Lysosomal diseases (LDs) are severe, progressive genetic disorders often asymptomatic at birth.
- Early diagnosis and intervention significantly improve patient outcomes for treatable LDs.
- Newborn screening (NBS) is crucial for timely detection and management of LDs.
Purpose of the Study:
- To pilot a newborn screening protocol for six lysosomal diseases in Brazil.
- To evaluate the feasibility of using tandem mass spectrometry for LDs detection.
- To establish a multi-tier testing strategy using dried blood spots.
Main Methods:
- Analyzed 20,066 unselected newborn dried blood spot (DBS) samples using MS/MS.
- Employed a multi-tier approach: enzyme assay (1st tier), biomarker analysis (2nd tier), and next-generation sequencing (3rd tier).
- All analyses were performed on the same DBS sample.
Main Results:
- 15 out of 20,066 newborns had enzyme activity below the cutoff.
- Two newborns were diagnosed with Fabry disease based on biochemical and molecular results.
- Five newborns showed biochemical results and carried pathogenic variants or VUS in GAA, suggesting potential Pompe disease.
Conclusions:
- Enzyme assay as a first-tier test yields a manageable number of positive results requiring further investigation.
- The ability to perform all tests on a single DBS sample supports scalability for NBS programs.
- This pilot study validates a cost-effective and efficient NBS strategy for lysosomal diseases.
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.
