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Implementation of Second-Tier Tests in Newborn Screening for Lysosomal Disorders in North Eastern Italy
Alberto B Burlina1, Giulia Polo1, Laura Rubert1
1Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening, Department of Women and Children's Health, University Hospital of Padova, Via Orus 2/B, 35129 Padova, Italy.
Insights
Newborn screening for four lysosomal storage diseases identified a combined incidence of 1 in 4497 births. A second-tier test significantly reduced false positives, enabling rapid diagnosis for conditions like Pompe disease.
Area of Science:
- Biochemistry
- Genetics
- Public Health
Background:
- Increasing availability of treatments and early intervention highlight the need for newborn screening for lysosomal storage diseases (LSDs).
- Lysosomal storage diseases are a group of rare genetic disorders that require timely diagnosis and management.
Purpose of the Study:
- To evaluate the effectiveness of a multiplexed tandem mass spectrometry (MS/MS) newborn screening program for four LSDs in North Eastern Italy.
- To determine the incidence of mucopolysaccharidosis type I, Pompe disease, Fabry disease, and Gaucher disease in a large newborn cohort.
- To assess the utility of a second-tier testing strategy in confirming positive newborn screening results.
Main Methods:
- A multiplexed tandem mass spectrometry (MS/MS) assay was used to screen 112,446 newborns for four LSDs.
- Neonates with initially low enzyme activity underwent a second dried blood spot collection for confirmation.
- Confirmatory testing and a second-tier test (except for Pompe disease) were employed to validate positive results.
Main Results:
- A total of 112,446 newborns were screened, with 0.12% recalled for a second sample and 0.06% showing low enzyme activity.
- Twenty-five neonates (0.02%) were true positives, including eight with Pompe disease, seven with Gaucher disease, eight with Fabry disease, and two with Mucopolysaccharidosis type I.
- The combined incidence of the four screened LSDs was 1 in 4497 births.
Conclusions:
- Newborn screening for multiple lysosomal storage diseases is feasible and identifies a significant number of affected infants.
- Implementing a second-tier testing approach effectively minimizes false-positive results, enhancing screening program efficiency.
- This combined approach facilitates early diagnosis and timely intervention for lysosomal storage diseases, improving patient outcomes.
Abstract:
The increasing availability of treatments and the importance of early intervention have stimulated interest in newborn screening for lysosomal storage diseases. Since 2015, 112,446 newborns in North Eastern Italy have been screened for four lysosomal disorders-mucopolysaccharidosis type I and Pompe, Fabry and Gaucher diseases-using a multiplexed tandem mass spectrometry (MS/MS) assay system. We recalled 138 neonates (0.12%) for collection of a second dried blood spot. Low activity was confirmed in 62 (0.06%), who underwent confirmatory testing. Twenty-five neonates (0.02%) were true positive: eight with Pompe disease; seven with Gaucher disease; eight with Fabry disease; and two with Mucopolysaccharidosis type I. The combined incidence of the four disorders was 1 in 4497 births. Except for Pompe disease, a second-tier test was implemented. We conclude that newborn screening for multiple lysosomal storage diseases combined with a second-tier test can largely eliminate false-positives and achieve rapid diagnosis.
