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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZRG1-GTIE-A (01))
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Sechi, Salvatore
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University of Washington
Schools of Arts and Sciences
United States
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Yi, Fan; Hong, Xinying; Kumar, Arun Babu et al. (2018) Detection of mucopolysaccharidosis III-A (Sanfilippo Syndrome-A) in dried blood spots (DBS) by tandem mass spectrometry. Mol Genet Metab 125:59-63
Hong, Xinying; Kumar, Arun Babu; Ronald Scott, C et al. (2018) Multiplex tandem mass spectrometry assay for newborn screening of X-linked adrenoleukodystrophy, biotinidase deficiency, and galactosemia with flexibility to assay other enzyme assays and biomarkers. Mol Genet Metab 124:101-108
Hong, Xinying; Gelb, Michael H (2018) One-step synthesis of carbon-13-labeled globotriaosylsphingosine (lyso-Gb3), an internal standard for biomarker analysis of Fabry disease. Mol Genet Metab 125:292-294
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Schielen, Peter C J I; Kemper, Evelien A; Gelb, Michael H (2017) Newborn Screening for Lysosomal Storage Diseases: A Concise Review of the Literature on Screening Methods, Therapeutic Possibilities and Regional Programs. Int J Neonatal Screen 3:
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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
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
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