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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Spacil, Zdenek; Babu Kumar, Arun; Liao, Hsuan-Chieh et al. (2016) Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples. Clin Chem 62:279-86
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
Kumar, Arun Babu; Masi, Sophia; Ghomashchi, Farideh et al. (2015) Tandem Mass Spectrometry Has a Larger Analytical Range than Fluorescence Assays of Lysosomal Enzymes: Application to Newborn Screening and Diagnosis of Mucopolysaccharidoses Types II, IVA, and VI. Clin Chem 61:1363-71
Kumar, Arun Babu; Spacil, Zdenek; Ghomashchi, Farideh et al. (2015) Fluorimetric assays for N-acetylgalactosamine-6-sulfatase and arylsulfatase B based on the natural substrates for confirmation of mucopolysaccharidoses types IVA and VI. Clin Chim Acta 451:125-8
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Ghomashchi, Farideh; Barcenas, Mariana; Turecek, Frantisek et al. (2015) Reliable Assay of Acid Sphingomyelinase Deficiency with the Mutation Q292K by Tandem Mass Spectrometry. Clin Chem 61:771-2
Barcenas, Mariana; Xue, Chang; Marushchak-Vlaskin, Tatyana et al. (2014) Tandem mass spectrometry assays of palmitoyl protein thioesterase 1 and tripeptidyl peptidase activity in dried blood spots for the detection of neuronal ceroid lipofuscinoses in newborns. Anal Chem 86:7962-8
Fitterer, Braden; Hall, Patricia; Antonishyn, Nick et al. (2014) Incidence and carrier frequency of Sandhoff disease in Saskatchewan determined using a novel substrate with detection by tandem mass spectrometry and molecular genetic analysis. Mol Genet Metab 111:382-9
Barcenas, Mariana; Suhr, Teryn R; Scott, C Ronald et al. (2014) Quantification of sulfatides in dried blood and urine spots from metachromatic leukodystrophy patients by liquid chromatography/electrospray tandem mass spectrometry. Clin Chim Acta 433:39-43

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