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Pilot neonatal screening program for lysosomal storage disorders, using lamp-1
E Ranierri1, R L Gerace, E M Ravenscroft
1Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia.
Insights
Lysosome associated membrane protein (LAMP-1) shows elevated levels in most lysosomal storage disorder patients. A new LAMP-1 blood spot assay is effective for newborn screening of these genetic disorders.
Area of Science:
- Biochemistry
- Genetics
- Neonatal Medicine
Background:
- Lysosomal storage disorders (LSDs) are a group of rare genetic diseases.
- Elevated lysosome associated membrane protein (LAMP-1) is observed in plasma of LSD patients.
- Newborn screening programs are crucial for early detection and intervention of genetic disorders.
Purpose of the Study:
- To develop and evaluate a first-tier screening assay for lysosomal storage disorders (LSDs) using LAMP-1 levels in newborn blood spots.
- To assess the effectiveness of LAMP-1 as a biomarker for neonatal screening of LSDs.
- To establish a prospective pilot newborn screening program for LSDs.
Main Methods:
- Development of a sandwich time-resolved fluorescent immunoassay for LAMP-1 detection.
- Utilized chicken polyclonal and mouse monoclonal antibodies for the LAMP-1 assay.
- Established stable and reproducible LAMP-1 blood-spot calibrators and quality control specimens.
- Conducted a prospective pilot Guthrie neonatal screening program involving 11,183 infants.
Main Results:
- The LAMP-1 assay demonstrated acceptable intra-assay (8.9% CV) and inter-assay (10% CV) variability.
- Screened 11,183 infants, establishing population distribution data for LAMP-1 levels.
- Median LAMP-1 level was 220 pg/l whole blood, with a 98th percentile of 483 µg/l whole blood.
Conclusions:
- The LAMP-1 immunoassay is a stable, reproducible, and effective first-tier screening tool for lysosomal storage disorders in newborns.
- The developed assay and pilot program demonstrate the feasibility of using LAMP-1 for neonatal screening of LSDs.
- Early identification of LSDs through newborn screening can facilitate timely management and improve patient outcomes.
Abstract:
We have demonstrated that the lysosome associated membrane protein (LAMP-1) is elevated in plasma from approximately 70% of lysosomal storage disorder patients. As part of the development of a newborn screening program for lysosomal storage disorders we have developed a first tier screening assay based upon the level of LAMP-I in blood spots taken from newborn Guthrie cards. To determine the effectiveness of the first-tier marker a prospective pilot Guthrie neonatal screening program for the identification of LSD was commenced in April 1998. Prior to commencement of the pilot program ethical approval was obtained and information leaflets regarding the neonatal screening of LSD were distributed to parents at the time of their infant's Guthrie collection. The LAMP-1 assay utilizes a chicken polyclonal and a mouse monoclonal in a sandwich time resolved fluorescent immunoassay. LAMP-1 blood-spot calibrators and quality control specimens were developed and shown to be stable and reproducible. To date 11,183 infants have been screened using LAMP-1. The population distribution is described with a median and 98th percentile of 220pg/l whole blood and 483microg/l whole blood respectively. Acceptable CV% for intra and inter assay of 8.9% and 10% respectively were obtained.