Free urinary glycosylated hydroxylysine as an indicator of altered collagen degradation in the mucopolysaccharidoses

Patel, Nina; Mills, Philippa; Davison, James; Cleary, Maureen; Gissen, Paul; Banushi, Blerida; Doykov, Ivan; Dorman, Megan; Mills, Kevin; Heywood, Wendy

doi:10.1002/jimd.12166

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…Heywood analyzed urine samples from GAG-positive MPS I, MPS II, and MPS VI patients by label-free proteomics, followed by a targeted proteomic multiple reaction monitoring LC-MS/MS assay; the study evidenced several differentially expressed proteins implicated in extracellular matrix organization, some of which allowed the researchers to differentiate between the MPS II neurological and non-neurological phenotype [244]. Later, the same group measured, by using the LC-MS/MS method, the levels of different forms of urinary hydroxylysine, as indicators of altered collagen metabolism and hence potential biomarkers of MPS disease [258]. A different proteomic approach based on two-dimensional gel electrophoresis combined with MALDI-TOF/TOF was used to identify the differential protein profile in the urine of MPS II patients [259].…”

Section: Disease Biomarkersmentioning

confidence: 99%

Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

D’Avanzo

Rigon

Zanetti

et al. 2020

IJMS

145

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Mucopolysaccharidosis type II (MPS II, Hunter syndrome) was first described by Dr. Charles Hunter in 1917. Since then, about one hundred years have passed and Hunter syndrome, although at first neglected for a few decades and afterwards mistaken for a long time for the similar disorder Hurler syndrome, has been clearly distinguished as a specific disease since 1978, when the distinct genetic causes of the two disorders were finally identified. MPS II is a rare genetic disorder, recently described as presenting an incidence rate ranging from 0.38 to 1.09 per 100,000 live male births, and it is the only X-linked-inherited mucopolysaccharidosis. The complex disease is due to a deficit of the lysosomal hydrolase iduronate 2-sulphatase, which is a crucial enzyme in the stepwise degradation of heparan and dermatan sulphate. This contributes to a heavy clinical phenotype involving most organ-systems, including the brain, in at least two-thirds of cases. In this review, we will summarize the history of the disease during this century through clinical and laboratory evaluations that allowed its definition, its correct diagnosis, a partial comprehension of its pathogenesis, and the proposition of therapeutic protocols. We will also highlight the main open issues related to the possible inclusion of MPS II in newborn screenings, the comprehension of brain pathogenesis, and treatment of the neurological compartment.

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Section: Disease Biomarkersmentioning

confidence: 99%

Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

D’Avanzo

Rigon

Zanetti

et al. 2020

IJMS

145

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“…Creatinine concentration was measured for each urine sample using mass spectrometry as previously described [ 48 ].…”

Section: Methodsmentioning

confidence: 99%

A Multiplexed Urinary Biomarker Panel Has Potential for Alzheimer’s Disease Diagnosis Using Targeted Proteomics and Machine Learning

Hällqvist,

Pinto,

Heywood

et al. 2023

IJMS

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As disease-modifying therapies are now available for Alzheimer’s disease (AD), accessible, accurate and affordable biomarkers to support diagnosis are urgently needed. We sought to develop a mass spectrometry-based urine test as a high-throughput screening tool for diagnosing AD. We collected urine from a discovery cohort (n = 11) of well-characterised individuals with AD (n = 6) and their asymptomatic, CSF biomarker-negative study partners (n = 5) and used untargeted proteomics for biomarker discovery. Protein biomarkers identified were taken forward to develop a high-throughput, multiplexed and targeted proteomic assay which was tested on an independent cohort (n = 21). The panel of proteins identified are known to be involved in AD pathogenesis. In comparing AD and controls, a panel of proteins including MIEN1, TNFB, VCAM1, REG1B and ABCA7 had a classification accuracy of 86%. These proteins have been previously implicated in AD pathogenesis. This suggests that urine-targeted mass spectrometry has potential utility as a diagnostic screening tool in AD.

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“…Regarding bone remodeling biomarkers, osteocalcin was found to be increased in children with MPS disorders, and BSAP and urinary PYD showed an increasing trend, which suggested increased osteoblast activity. Plasma IL-1β, TNF-α, and D-PYR (which were higher in MPSIthan in controls [ 58 ] and IL-6 might also be appropriate biomarkers to monitor progression in joint contracture, short stature, and hip dysplasia over time [ 59 ] ( Table 2 ).…”

Section: Biomarkers Related To Bone Metabolism In Mpsmentioning

confidence: 99%

“…Patel et al recently reported that urinary-free hydroxylated (Lys-OH) and glycosylated hydroxylysines (Lys-O-Gal and Lys-O-GalGlc) in MPS patients measured by tandem liquid chromatography-tandem mass spectrometry assay were indicators of altered collagen degradation [ 59 ]. These are unique and specific post-translational modifications of collagen [ 63 ].…”

Section: Biomarkers Related To Bone Metabolism In Mpsmentioning

confidence: 99%

“…Lys-O-Gal is predominantly found in bone tissues, and Lys-O-GalGlc is mainly found in the skin [ 65 ]. The ratio of Lys-O-Gal to Lys-O-GalGlc has also been examined as an indicator of the source of collagen degradation; it was found to be significantly higher in all pediatric MPS I, II, and IV patients, with a small significant increase in adult MPS IV patients [ 59 ] ( Table 2 ). However, the authors concluded that the collagen degradation products originated from a source other than bone, such as cartilage or connective tissue [ 59 ].…”

Section: Biomarkers Related To Bone Metabolism In Mpsmentioning

confidence: 99%

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Bone Biomarkers in Mucopolysaccharidoses

Nakamura-Utsunomiya

2021

IJMS

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The accumulation of glycosaminoglycans (GAGs) in bone and cartilage leads to progressive damage in cartilage that, in turn, reduces bone growth by the destruction of the growth plate, incomplete ossification, and growth imbalance. The mechanisms of pathophysiology related to bone metabolism in mucopolysaccharidoses (MPS) include impaired chondrocyte function and the failure of endochondral ossification, which leads to the release of inflammatory cytokines via the activation of Toll-like receptors by GAGs. Although improvements in the daily living of patients with MPS have been achieved with enzyme replacement, treatment for the bone disorder is limited. There is an increasing need to identify biomarkers related to bone and cartilage to evaluate the progressive status and to monitor the treatment of MPS. Recently, new analysis methods, such as proteomic analysis, have identified new biomarkers in MPS. This review summarizes advances in clinical bone metabolism and bone biomarkers.

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Free urinary glycosylated hydroxylysine as an indicator of altered collagen degradation in the mucopolysaccharidoses

Cited by 10 publications

References 28 publications

Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

A Multiplexed Urinary Biomarker Panel Has Potential for Alzheimer’s Disease Diagnosis Using Targeted Proteomics and Machine Learning

Bone Biomarkers in Mucopolysaccharidoses

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