Urinary Glycosaminoglycans in Newborns: Correlation with Gestational Age

Hassan, Mostafa S.; Reale, M; Rosenfeld, Louis

doi:10.1203/00006450-199904020-00318

Cited by 1 publication

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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: 69%

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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