The unifying goal of the proposed studies is the development of assays for the multiplex analysis of enzyme activities of diagnostic value for the detection of inborn errors of metabolism. The assays are based on quantitative analysis of enzymatic products by tandem mass spectrometry as a common analytical platform. In the previous 3-year funding period we have developed tandem mass spectrometric assays for several lysosomal storage diseases using dried blood spots on newborn screening cards. We have also developed mass spectrometric assays for the clinical detection of three porphyrias. Our research on tandem mass spectrometric assays of lysosomal storage diseases has already had a significant impact on the medical community, and some of the assays we developed have been transitioned from our lab to several newborn screening labs in the U.S. and worldwide. The proposed research aims at the detection of syndromes of Hunter, Maroteaux-Lamy, Morquio A, Metachromatic Leukodystrophy, and Sanfilippo A-D using dried blood spots on newborn screening cards. Treatments for these lysosomal storage disorders are either available or being developed and our assays will make it possible for newborn screening laboratories to detect these diseases prior to the development of irreversible symptoms. Also proposed is a continuation of studies of porphyria-linked enzymes aminolevulinic acid dehydratase, porphobilinogen oxidase, and ferrochelatase to develop a complete battery of assays for porphyrias based on tandem mass spectrometry.
The proposed research is aimed at the development of selective and sensitive methods based on enzyme assays and product analysis by tandem mass spectrometry. Technologies and procedures for the early detection of several lysosomal storage diseases are proposed in continuation of our previous successful efforts in this area.
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|Liao, Hsuan-Chieh; Spacil, Zdenek; Ghomashchi, Farideh et al. (2017) Lymphocyte Galactocerebrosidase Activity by LC-MS/MS for Post-Newborn Screening Evaluation of Krabbe Disease. Clin Chem 63:1363-1369|
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|Liao, Hsuan-Chieh; Chan, Min-Ju; Yang, Chia-Feng et al. (2017) Mass Spectrometry but Not Fluorimetry Distinguishes Affected and Pseudodeficiency Patients in Newborn Screening for Pompe Disease. Clin Chem 63:1271-1277|
|Orsini, Joseph J; Saavedra-Matiz, Carlos A; Gelb, Michael H et al. (2016) Newborn screening for Krabbe's disease. J Neurosci Res 94:1063-75|
|Elliott, Susan; Buroker, Norman; Cournoyer, Jason J et al. (2016) Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry. Mol Genet Metab 118:304-9|
|Peake, Roy W A; Marsden, Deborah L; Bodamer, Olaf A et al. (2016) Newborn Screening for Lysosomal Storage Disorders: Quo Vadis? Clin Chem 62:1430-1438|
|Elliott, Susan; Buroker, Norman; Cournoyer, Jason J et al. (2016) Dataset and standard operating procedure for newborn screening of six lysosomal storage diseases: By tandem mass spectrometry. Data Brief 8:915-24|
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