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Published on: March 13, 2015
Development of Dried Blood Spot Proficiency Testing Materials for Newborn Screening of Lysosomal Diseases Using
Elya Courtney1, Samantha L Isenberg1, Timothy Lim1
1Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
Insights
New recombinant enzyme methods create improved quality control materials for newborn screening of lysosomal diseases (LDs). This advancement enhances proficiency testing and supports international expansion of newborn screening programs for these rare conditions.
Area of Science:
- Biochemistry and Molecular Biology
- Clinical Diagnostics and Laboratory Medicine
- Public Health and Newborn Screening
Background:
- Lysosomal diseases (LDs) are increasingly recognized in newborn screening, necessitating expanded proficiency testing (PT) capabilities.
- Existing PT materials for LDs face limitations in scalability and supporting a growing number of screened conditions.
- The Recommended Uniform Screening Panel has recently included mucopolysaccharidosis type II (MPS-II) and Infantile Krabbe disease, highlighting the need for broader LD screening.
Purpose of the Study:
- To develop and validate a novel manufacturing process for producing high-performing, dried blood spot-based PT materials for multiple LDs.
- To utilize recombinant enzymes for creating first-tier PT materials for mucopolysaccharidosis type I, MPS-II, Gaucher, Fabry, Krabbe, Pompe, and Niemann-Pick A/B.
- To expand the CDC's Newborn Screening Quality Assurance Program (NSQAP) LD PT panel to include four additional LDs.
Main Methods:
- Development of a new manufacturing process using recombinant enzymes for LD PT materials.
- Iterative testing phases including prototype, pilot, and external validation with up to 31 laboratories.
- Evaluation of PT materials using common newborn screening methods: tandem mass spectrometry (LC and FI), digital microfluidics, and fluorometric assays.
Main Results:
- A novel, scalable manufacturing process for dried blood spot-based LD PT specimens was successfully developed.
- The new PT materials demonstrated high performance across various analytical methods used in newborn screening.
- The process enabled international expansion of NSQAP LD PT enrollment and supports future panel growth.
Conclusions:
- The developed recombinant enzyme-based manufacturing process offers significant advantages over previous methods relying on patient-derived cell lines.
- This innovation enhances the scalability and accessibility of PT for LDs, facilitating broader newborn screening efforts.
- The updated specimens and expanded NSQAP program, launched in January 2025, will improve quality assurance for an increasing number of LDs.
Abstract:
Lysosomal diseases (LDs, or Lysosomal Storage Disorders) have become increasingly visible in the newborn screening community, with the addition of mucopolysaccharidosis type II (MPS-II) into the Recommended Uniform Screening Panel in August 2022 and Infantile Krabbe disease in June 2024. As more LDs are expected to be considered for screening adoption, the ability to multiplex conditions and expand proficiency testing (PT) using quality control materials is essential. This study examines the use of recombinant enzymes to produce first-tier PT materials for mucopolysaccharidosis type I, MPS-II, Gaucher, Fabry, Krabbe, Pompe, and Niemann-Pick A/B (acid sphingomyelinase deficiency)-adding four disorders to the CDC's Newborn Screening Quality Assurance Program (NSQAP) LD PT panel. Through an iterative process that included two prototype phases, two pilot phases, and external testing by up to 31 external laboratories, a new manufacturing process was developed for producing high-performing dried blood spot-based LD PT specimens. Materials were evaluated using several methods commonly employed by newborn screening laboratories, including tandem mass spectrometry with flow injection and liquid chromatography, digital microfluidics, and fluorometric assays. This novel process for producing LD PT materials offers several advantages over previous manufacturing methods that relied on immortalized cell lines from affected patients. Improved scalability, for example, has enabled NSQAP to expand LD PT enrollment internationally. Furthermore, the new process makes it easier to support future expansions of the LD screening panel. The updated specimens and expanded program were launched in January 2025.
