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

  • Jyotsna VermaEmail author
  • Divya C. Thomas
  • David C. Kasper
  • Sandeepika Sharma
  • Ratna D. Puri
  • Sunita Bijarnia-Mahay
  • Pramod K. Mistry
  • Ishwar C. Verma
Research Report
Part of the JIMD Reports book series (JIMD, volume 31)

Abstract

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

Keywords

Diagnostic accuracy Dried blood spots Enzymatic diagnosis Lysosomal enzymes Lysosomal storage disorders Molecular diagnosis 

Abbreviations

CK

Creatine phosphokinase

DBS

Dried blood spot

EQAS

External Quality Assurance Scheme

ERNDIM

European Research Network for evaluation and improvement of screening, diagnosis, and treatment of inborn errors of metabolism

GAGs

Glycosaminoglycans

LSDs

Lysosomal storage disorders

MPS

Mucopolysaccharidosis

Notes

Acknowledgement

We thank all patients and normal subjects whose blood was used as a control/reference material to generate the data for this study. We extend our thanks to Genzyme (India) who has chosen our center as a referral laboratory for lysosomal enzymes testing. We express our gratitude to doctors from India and neighboring countries for referring patients to our genetic center. We appreciate Genzyme (India), a Sanofi company for extending support to patients for testing and treatment. We also thank Chairman and Director Administration, Sir Ganga Ram Hospital, for their cooperation in setting up genetic testing facility.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jyotsna Verma
    • 1
    Email author
  • Divya C. Thomas
    • 1
  • David C. Kasper
    • 2
  • Sandeepika Sharma
    • 1
  • Ratna D. Puri
    • 1
  • Sunita Bijarnia-Mahay
    • 1
  • Pramod K. Mistry
    • 3
  • Ishwar C. Verma
    • 1
  1. 1.Biochemical Genetics, Centre of Medical Genetics, Sir Ganga Ram HospitalNew DelhiIndia
  2. 2.Clinical Institute of Laboratory MedicineMedical University of ViennaViennaAustria
  3. 3.Department of Internal Medicine (Digestive Diseases)Yale University School of MedicineNew HavenUSA

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