Urinary Glycosaminoglycan Estimation as a Routine Clinical Service

Dave, Mihika B.; Chawla, Prerna K.; Dherai, Alpa J.; Ashavaid, Tester F.

doi:10.1007/s12291-014-0456-y

Cited by 8 publications

(9 citation statements)

References 11 publications

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“…Despite this early decrease, levels of HS and HS-NRE in CSF and urine of MPS IIIB dogs at these later time points remain elevated in comparison to the levels present in unaffected dogs of any time point. High levels of urinary GAGs have been reported previously in healthy newborn humans and have been suggested to be associated with increased turnover of extracellular matrix during development [22][23][24] . Elevated levels of HS and HS-NRE in the CSF and urine of 1-month old MPS IIIB dogs could be indicative of the ongoing brain growth and increased turnover of extracellular matrix that occurs during this time period 25 .…”

Section: Discussionmentioning

confidence: 67%

Central nervous system pathology in preclinical MPS IIIB dogs reveals progressive changes in clinically relevant brain regions

Egeland

Tarczyluk-Wells

Asmar

et al. 2020

Sci Rep

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Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B) is an autosomal recessive lysosomal storage disorder caused by the deficiency of alpha-N-acetylglucosaminidase activity, leading to increased levels of nondegraded heparan sulfate (HS). A mouse model has been useful to evaluate novel treatments for MPS IIIB, but has limitations. In this study, we evaluated the naturally occurring canine model of MPS IIIB for the onset and progression of biochemical and neuropathological changes during the preclinical stages (onset approximately 24–30 months of age) of canine MPS IIIB disease. Even by 1 month of age, MPS IIIB dogs had elevated HS levels in brain and cerebrospinal fluid. Analysis of histopathology of several disease-relevant regions of the forebrain demonstrated progressive lysosomal storage and microglial activation despite a lack of cerebrocortical atrophy in the oldest animals studied. More pronounced histopathology changes were detected in the cerebellum, where progressive lysosomal storage, astrocytosis and microglial activation were observed. Microglial activation was particularly prominent in cerebellar white matter and within the deep cerebellar nuclei, where neuron loss also occurred. The findings in this study will form the basis of future assessments of therapeutic efficacy in this large animal disease model.

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Section: Discussionmentioning

confidence: 67%

Central nervous system pathology in preclinical MPS IIIB dogs reveals progressive changes in clinically relevant brain regions

Egeland

Tarczyluk-Wells

Asmar

et al. 2020

Sci Rep

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“… 4 , 14 Irrespective of the method used to quantify GAGs in urine, the interpretation of the results can be complicated by the age-specific reference ranges. 15 …”

Section: Laboratory Role In Diagnosis and Treatment Of Mps Ivamentioning

confidence: 99%

A 9-Month-Old with Skeletal Abnormalities and a Consanguineous Sibling with Mucopolysaccharidosis IVA: The Role of Urinary Glycosaminoglycan Testing in Disease Diagnosis and Treatment Monitoring

Goldman

Dietz

et al. 2021

Clin Med Insights Case Rep

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Mucopolysaccharidosis IVA (MPS IVA) is a rare autosomal recessive lysosomal storage disorder resulting from N-acetylgalactosamine-6-sulfatase (GALNS) deficiency that occurs in approximately 1 in 76 000 to 1 in 640 000 live births. Given that the diagnosis of MPS IVA relies heavily on the results of initial urine glycosaminoglycan (GAG) screening, cases that present with falsely normal urine GAG concentrations can delay the diagnosis and follow-up care for patients. This case study follows a patient diagnosed with MPS IVA at 9 months of age based on relation to a consanguineous 3-year-old sibling with MPS IVA and the use of direct enzyme activity analysis. Details regarding skeletal presentation and identification of genetic variants are presented along with data on follow-up urinary GAG monitoring during treatment with enzyme replacement therapy and treatment for a growth hormone disorder.

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“…This pattern is similar to that observed for urinary GAGs. 7,8 Most urinary markers normalized to creatinine decrease with age, reflecting a change in relative muscle mass to body mass ratio with age.…”

Section: Initial Investigations Of Modified Lysine In a Test Cohortmentioning

confidence: 99%

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

Patel

Mills

Davison

et al. 2019

J of Inher Metab Disea

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Extracellular matrix (ECM) disruption is known to be an early pathological feature of the Mucopolysaccharidoses (MPS). Collagen is the main component of the ECM and its metabolism could act as a useful indicator of ECM disruption. We have measured the specific collagen breakdown products; urinary free hydroxylated (Lys‐OH) and glycosylated hydroxylysines (Lys‐O‐Gal and Lys‐O‐GalGlc) in MPS patients using a tandem liquid chromatography tandem mass spectrometry assay. A pilot study cohort analysis indicated that concentrations of lysine and Lys‐OH were raised significantly in MPS I (Hurler) disease patients. Lys‐O‐GalGlc was raised in MPS II and MPS VI patients and demonstrated a significant difference between MPS I Hurler and an MPS I Hurler‐Scheie group. Further analysis determined an age association for glycosylated hydroxylysine in control samples similar to that observed for the glycosaminoglycans. Using defined age ranges and treatment naïve patient samples we confirmed an increase in glycosylated hydroxylysines in MPS I and in adult MPS IVA. We also looked at the ratio of Lys‐O‐Gal to Lys‐O‐GalGlc, an indicator of the source of collagen degradation, and noticed a significant change in the ratio for all pediatric MPS I, II, and IV patients, and a small significant increase in adult MPS IV. This indicated that the collagen degradation products were coming from a source other than bone such as cartilage or connective tissue. To see how specific the changes in glycosylated hydroxylysine were to MPS patients we also looked at levels in patients with other inherited metabolic disorders. MPS patients showed a trend towards increased glycosylated hydroxylysines and an elevated ratio compared to other metabolic disorders that included Battens disease, Fabry disease, Pyridoxine‐dependent epilepsy (due to mutations in ALDH7A1), and Niemann Pick C disease.

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Urinary Glycosaminoglycan Estimation as a Routine Clinical Service

Cited by 8 publications

References 11 publications

Central nervous system pathology in preclinical MPS IIIB dogs reveals progressive changes in clinically relevant brain regions

Central nervous system pathology in preclinical MPS IIIB dogs reveals progressive changes in clinically relevant brain regions

A 9-Month-Old with Skeletal Abnormalities and a Consanguineous Sibling with Mucopolysaccharidosis IVA: The Role of Urinary Glycosaminoglycan Testing in Disease Diagnosis and Treatment Monitoring

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

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