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Mol Genet Metab. 2009 Dec;98(4):406-11. doi: 10.1016/j.ymgme.2009.07.015. Epub 2009 Aug 5.

Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II.

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Division of Metabolic Disorders, Pediatric Subspecialty Faculty, CHOC Children's, Orange, CA 92868, USA.



The mucopolysaccharidoses (MPSs) are a family of lysosomal storage disorders caused by impaired glycosaminoglycan degradation. Characteristic brain imaging abnormalities are seen in MPS patients. This study aims to determine the effects of hematopoietic stem cell transplantation (HSCT) and/or intravenous enzyme replacement therapy (ERT) on these abnormalities.


A retrospective chart and brain imaging study review was conducted of MPS types I and II patients with brain magnetic resonance imaging (MRI) performed at, and following, initiation of treatment. White matter abnormalities, dilated perivascular spaces, corpus callosal abnormalities, and ventriculomegaly were scored by three independent neuroradiologists blinded to cognitive status, date of treatment initiation, and type(s) of treatment.


Five patients were identified: three patients with MPS I and two with MPS II. Duration of follow-up ranged from 13 to 51 months. One patient had severe MPS I (genotype W402X/35del12) and received ERT followed by HSCT. The remaining patients had ERT only. The other two MPS I patients were cognitively normal siblings (genotype P533R/P533R) with an intermediate phenotype. One MPS II patient had moderate cognitive impairment without regression (genotype 979insAGCA); the other (genotype R8X) had normal cognition. There was very little inter-observer variation in MRI scoring. The greatest abnormalities for each patient were found at initial MRI. All patients, including the ERT-only patients, demonstrated improved or unchanged MRI scores following treatment. Severity of white matter abnormalities or dilated perivascular spaces did not correlate with cognitive impairment; as such, extensive pre-treatment MRI abnormalities were noted in the older, cognitively normal MPS I sibling. In comparison, his younger sibling had only mild MRI abnormalities at the same age, after receiving 4 years of ERT.


This study represents one of the first to document the CNS effects of ERT in MPS patients utilizing serial brain MR imaging studies, and raises several important observations. Brain MRI abnormalities typically become more pronounced with age; initiation of ERT or HSCT reversed or stabilized this trend in the MPS patients studied. In addition, earlier initiation of treatment resulted in decreased severity of imaging abnormalities. Possible mechanisms for these observations include improved cerebrospinal fluid dynamics, reduced central nervous system glycosaminoglycan storage via efflux through the blood-brain barrier (BBB), repair of damaged BBB, reduction in CNS inflammation, or ERT permeability through the BBB.

[Indexed for MEDLINE]

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