Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses

Girisha, KM (2016) Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses. Molecular Genetics and Metabolism, 120 (3). pp. 247-254. ISSN 1096-7192

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Abstract

Mucopolysaccharidoses (MPSs) and mucolipidoses (ML) are groups of lysosomal storage disorders in which lysosomal hydrolases are deficient leading to accumulation of undegraded glycosaminoglycans (GAGs), throughout the body, subsequently resulting in progressive damage to multiple tissues and organs. Assays using tandem mass spectrometry (MS/MS) have been established to measure GAGs in serum or plasma from MPS and ML patients, but few studies were performed to determine whether these assays are sufficiently robust to measure GAG levels in dried blood spots (DBS) of patients with MPS and ML. Material and methods: In this study,we evaluated GAG levels in DBS samples from124MPS andML patients (MPS I=16; MPS II=21; MPS III=40; MPS IV=32; MPS VI=10; MPS VII=1; ML=4), and compared themwith 115 age-matched controls. Disaccharides were produced frompolymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Subsequently, dermatan sulfate (DS), heparan sulfate (HS-0S, HS-NS), and keratan sulfate (mono-sulfated KS, di-sulfated KS, and ratio of di-sulfated KS in total KS) were measured by MS/MS. Results: Untreated patients with MPS I, II, VI, and ML had higher levels of DS compared to control samples. Untreated patients with MPS I, II, III, VI, and ML had higher levels of HS-0S; and untreated patients with MPS II, III and VI and ML had higher levels of HS-NS. Levels of KSwere age dependent, so although levels of both mono-sulfated KS and di-sulfated KSwere generally higher in patients, particularly forMPS II andMPS IV, age group numbers were not sufficient to determine significance of such changes. However, the ratio of di-sulfated KS in total KS was significantly higher in all MPS patients younger than 5 years old, compared to age-matched controls. MPS I and VI patients treated with HSCT had normal levels of DS, and MPS I, VI, and VII treated with ERT or HSCT had normal levels of HS-0S and HS-NS, indicating that both treatments are effective in decreasing blood GAG levels. Conclusion: Measurement of GAG levels in DBS is useful for diagnosis and potentially for monitoring the therapeutic efficacy in MPS.

Item Type: Article
Uncontrolled Keywords: Mucopolysaccharidoses; mucolipidoses; glycosaminoglycans; tandem mass spectrometry; hematopoietic stem cell transplantation.
Subjects: Medicine > KMC Manipal > Paediatrics
Depositing User: KMC Library
Date Deposited: 27 Mar 2017 04:23
Last Modified: 27 Mar 2017 04:23
URI: http://eprints.manipal.edu/id/eprint/148573

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