Inherited Metabolic Disorders: Efficacy of Enzyme Assays on Dried Blood Spots for the Diagnosis of Lysosomal Storage Disorders

• DOI: 10.1007/8904_2016_548
• Publication Date: 2016-03-23T07:51:19Z
• Authors: Jyotsna Verma; Divya C. Thomas; David C. Kasper; Sandeepika Sharma; Ratna D. Puri; Sunita Bijarnia-M...; Pramod K. Mistry; Ishwar C. Verma
• Keywords: Concordance; Dried blood spot; Lysosomal Storage Disorders; Mucopolysaccharidosis I; Mucopolysaccharidosis; Sandhoff disease; Gangliosidosis; Dried blood; Lysosomal storage disease; Mucopolysaccharidosis type II; Neuronal ceroid lipofuscinosis

High consanguinity rates, poor access to accurate diagnostic tests, and costly therapies are the main causes of increased burden lysosomal storage disorders (LSDs) in developing countries. Therefore, there is a major unmet need for economical tests facilitate diagnosis consideration before irreversible complications occur. In cross-country study, we utilized dried blood spots (DBS) 1,033 patients clinically suspected harbor LSDs enzymatic using modified fluorometric assays from March 2013 through May 2015. Results were validated by demonstrating reproducibility, testing different sample types (leukocytes/plasma/skin fibroblast), mutation or measuring specific biomarkers. Thirty percent (307/1,033) confirmed have one tested. Reference intervals established unambiguously identified affected patients. Correlation DBS results with other biological samples (n = 172) studies 74) demonstrated 100% concordance Gaucher, Fabry, Tay Sachs, Sandhoff, Niemann-Pick, GM1, Neuronal ceroid lipofuscinosis (NCL), Fucosidosis, Mannosidosis, Mucopolysaccharidosis (MPS) II, IIIb, IVa, VI, VII, I-Cell diseases, 91.4% 88% Pompe MPS-I, respectively. Gaucher most common India Pakistan, followed MPS-I both Sri Lanka. Study demonstrates utility reliable LSDs. Diagnostic accuracy (97.6%) confirms veracity enzyme assays. Adoption will overcome significant hurdles transportation remote regions. molecular should become standard care make timely diagnosis, develop personalized treatment/monitoring plan, genetic counseling.