The goal of this project is to design and prepare diagnostic biomarker reference standards for theendogenous glycosaminoglycan (GAG) Mucopolysaccharidosis type I (MPS-I) and type II (MPS-II) biomarkers. MPS-I and MPS-II are lysosomal storage disorders (LSDs) which are listed on theRecommended Uniform Screening Panel (RUSP) in the United States and are included in globalNewborn Screening (NBS) programs and Pilot studies currently ongoing. One issue with the first-tier enzyme activity screening is the high prevalence of false positives, which may be eliminatedby second-tier biomarker screening. The endogenous GAG biomarker method has been shownin recent studies to provide accurate discrimination of diagnosed newborns from the referencerange of healthy newborns and newborns with pseudodeficiencies (for MPS-II). Additionally, bythis method unique biomarkers have been identified for each disease, which will aid diagnosticlabs in clinical evaluation. Currently, no chemically identical, quantified reference standards(which meets recommendations from FDA guidance on bioanalytical method validation) areavailable on the market. The GAG disaccharide internal standards prepared within the scope ofthis project will meet the reference standard recommendations indicated by the FDA, which arenot currently met by any other product on the market. As a result, GelbChem will be the firstsupplier of all materials needed to complete bioanalytical validation of the endogenous GAGbiomarker method for MPS-I and MPS-II.
Public Health Relevance Statement: Project narrative:
Newborn screening for treatable lysosomal storage diseases is warranted since initiation of
treatment soon after birth leads to a better treatment outcome. Our research team has developed
technology for newborn screening of a series of lysosomal storage diseases which is
commercialized by our business branch (GelbChem, LLC). This proposal aims to develop and
provide certified standards for a new biomarker assay for second-tier screening and clinical
diagnosis of the genetic diseases MPS-I and MPS-II.
Project Terms: <0-4 weeks old><α-L-iduronidase (IDA, IDUA) deficiency>
