Abstract
Lysosomal storage disorders (LSDs) are considered to be a rare metabolic disease for the national health forum, clinicians, and scientists. This study aimed to know the prevalence of different LSDs, their geographical variation, and burden on the society. It included 1,110 children from January 2002 to December 2012, having coarse facial features, hepatomegaly or hepatosplenomegaly, skeletal dysplasia, neuroregression, leukodystrophy, developmental delay, cerebral-cerebellar atrophy, and abnormal ophthalmic findings. All subjects were screened for I-cell disease, glycolipid storage disorders (Niemann-Pick disease A/B, Gaucher), and mucopolysaccharide disorders followed by confirmatory lysosomal enzymes study from leucocytes and/or fibroblasts. Niemann-Pick disease-C (NPC) was confirmed by fibroblasts study using filipin stain. Various storage disorders were detected in 387 children (34.8 %) with highest prevalence of glycolipid storage disorders in 48 %, followed by mucopolysaccharide disorders in 22 % and defective sulfatide degradation in 14 % of the children. Less common defects were glycogen degradation defect and protein degradation defect in 5 % each, lysosomal trafficking protein defect in 4 %, and transport defect in 3 % of the patients. This study demonstrates higher incidence of Gaucher disease (16 %) followed by GM2 gangliosidosis that includes Tay-Sachs disease (10 %) and Sandhoff disease (7.8 %) and mucopolysaccharide disorders among all LSDs. Nearly 30 % of the affected children were born to consanguineous parents and this was higher (72 %) in children with Batten disease. Our study also demonstrates two common mutations c.1277_1278insTATC in 14.28 % (4/28) and c.964G>T (p.D322Y) in 10.7 % (3/28) for Tay-Sachs disease in addition to the earlier reported c.1385A>T (p.E462V) mutation in 21.42 % (6/28).
Competing interests: None declared
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Acknowledgments
We sincerely acknowledge the work of Meikle PJ, Pinto R, and Poupetova H and their colleagues from Australia, Portugal, and Czech Republic, respectively, whose publications were of immense help in the preparation of this manuscript. We are grateful to all the referring doctors and patients for their support without whose consent, this study could not have been possible and Indian Council of Medical Research (ICMR) for providing financial support to carry out this study.
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Communicated by: Verena Peters
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Synopsis
This cross-sectional study provides an up-to-date description of the current scenario of different lysosomal storage disorders (LSDs) and its burden on the society and highlights the common mutation spectrum for Tay-Sachs disease in India.
Conflict of Interest
The authors declare that they have no conflict of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
Details of the Contributions of Individual Authors
JS designed the experiment and standardized the protocols. MM, NO, and CA were involved in processing of the samples. MJ provided the technical guidelines. RS, AB, KG, NN, CD, MK, and SM were involved in collection of the clinical details. MM, JS, and FS prepared the manuscript. All the authors read and approved the manuscript.
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Sheth, J. et al. (2013). Burden of Lysosomal Storage Disorders in India: Experience of 387 Affected Children from a Single Diagnostic Facility. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Volume 12. JIMD Reports, vol 12. Springer, Cham. https://doi.org/10.1007/8904_2013_244
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DOI: https://doi.org/10.1007/8904_2013_244
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