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01-10-2017 | Original Article

Serum global metabolomics profiling reveals profound metabolic impairments in patients with MPS IIIA and MPS IIIB

Authors: Haiyan Fu, Aaron S. Meadows, Ricardo J. Pineda, Robert P. Mohney, Steve Stirdivant, Douglas M. McCarty

Published in: Metabolic Brain Disease | Issue 5/2017

Abstract

The monogenic defects in specific lysosomal enzymes in mucopolysaccharidosis (MPS) III lead to lysosomal storage of glycosaminoglycans and complex CNS and somatic pathology, for which the detailed mechanisms remain unclear. In this study, serum samples from patients with MPS IIIA (age 2-9 yr) and MPS IIIB (2-13 yr) and healthy controls (age 2-9 yr) were assayed by global metabolomics profiling of 658 metabolites using mass spectrometry. Significant alterations were detected in 423 metabolites in all MPS III patients, of which 366 (86.5%) decreased and 57 (13.5%) increased. Similar profiles were observed when analyzing data from MPS IIIA and MPS IIIB samples separately, with only limited age variations in 36 metabolites. The observed metabolic disturbances in MPS III patients involve virtually all major pathways of amino acid (101/150), peptide (17/21), carbohydrate (19/23), lipid (221/325), nucleotide (15/25), energy (8/9), vitamins and co-factors (8/21), and xenobiotics (34/84) metabolism. Notably, detected serum metabolite decreases involved all key amino acids, all major neurotransmitter pathways, and broad neuroprotective compounds. The elevated metabolites are predominantly lipid derivatives, and also include cysteine metabolites and a fibrinogen peptide fragment, consistent with the status of oxidative stress and inflammation in MPS III. This study demonstrates that the lysosomal glycosaminoglycans storage triggers profound metabolic disturbances in patients with MPS III disorders, leading to severe functional depression of virtually all metabolic pathways, which emerge early during the disease progression. Serum global metabolomics profiling may provide an important and minimally invasive tool for better understanding the disease mechanisms and identification of potential biomarkers for MPS III.

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Title: Serum global metabolomics profiling reveals profound metabolic impairments in patients with MPS IIIA and MPS IIIB
Authors: Haiyan Fu
Aaron S. Meadows
Ricardo J. Pineda
Robert P. Mohney
Steve Stirdivant
Douglas M. McCarty
Publication date: 01-10-2017
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 5/2017
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-017-0009-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Serum global metabolomics profiling reveals profound metabolic impairments in patients with MPS IIIA and MPS IIIB

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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