Restoration of normal lysosomal function in mucopolysaccharidosis type VII cells by retroviral vector-mediated gene transfer.
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Retroviral vectors were constructed containing a rat beta-glucuronidase cDNA driven by heterologous promoters. Vector-mediated gene transfer into human and canine beta-glucuronidase-deficient mucopolysaccharidosis type VII fibroblasts completely corrected the deficiency in beta-glucuronidase enzymatic activity. In primary cultures of canine mucopolysaccharidosis type VII retinal pigment epithelial cells, which contain large amounts of undegraded glycosaminoglycan substrates, vector correction restored normal processing of specific glycosaminoglycans in the lysosomal compartment. In canine mucopolysaccharidosis type VII bone marrow cells, beta-glucuronidase was expressed at high levels in transduced cells. Thus, the vector-encoded beta-glucuronidase was expressed at therapeutic levels in the appropriate organelle and corrected the metabolic defect in cells exhibiting the characteristic pathology of this lysosomal storage disorder. (+info)
Multidetector computed tomography (MDCT) for preoperative airway assessment in children with mucopolysaccharidoses.
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BACKGROUND: Accumulation of glycosaminoglycans is known to cause significant problems in the anesthetic management of children with mucopolysaccharidoses (MPS). Clinical and standard radiological evaluation may convey insufficient information about the upper airway and trachea in children with MPS. Multidetector computed tomography (MDCT) images have been used to define the central airway and previous studies have recommended this tool to assess the airway of children who are considered at risk of difficult intubation. However, MDCT has not been recommended in MPS children. The aim of this clinical scenario study was to verify whether information from MDCT reconstruction of the airway is useful in airway management planning of children with MPS. METHODS: In a two phase questionnaire-based study, 26 pediatric anesthesiologists were asked to produce airway management plans for 5 children with MPS. An initial plan for airway control was reported after assessment of standard preoperative anesthetic charts. A subsequent airway strategy was then described after reviewing tracheal MDCT images of each patient. RESULTS: MDCT images provided additional clinically-relevant information in 87% (95% CI: 79-92%) of the evaluations. Reduction of tracheal size was the most common finding provided by the MDCT images. After reviewing the MDCT images, anesthesiologists changed their primary airway device selection in 21% of the evaluations (P=0.01). CONCLUSION: Airway reconstruction using MDCT images from a previous CT scan may provide a useful assessment tool for preoperative airway evaluation and planning in MPS children. (+info)
Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management.
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Neuroimaging findings in patient series with mucopolysaccharidosis.
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INTRODUCTION: Mucopolysaccharidoses (MPS) are a group of inherited disorders due to lysosomal enzyme deficiencies. The aims of this study are to describe the neuroimaging findings in children evaluated in our hospital with this diagnosis, looking for a possible correlation of these alterations with the type of MPS and clinical severity, and finally to compare these findings with those previously reported. MATERIAL AND METHODS: We retrospectively analysed the medical records of 19 patients who had been diagnosed with MPS between 1992 and 2010: 7 had type I (5 with Hurler syndrome and 2 with Hurler-Scheie syndrome), 10 had type II or Hunter syndrome (4 with the severe form and 6 with the mild form), 1 had type III or Sanfilippo syndrome and 1 had type VI or Maroteaux-Lamy syndrome. We assessed the brain neuroimaging studies: computed axial tomography (CAT) in 5 patients, and magnetic resonance imaging (MRI) in 15. RESULTS: We observed a broad spectrum of neuroimaging anomalies. In CAT: mega cisterna magna (3/5, 60%). In brain MRI: dilated Virchow-Robin perivascular spaces (11/15, 73%), white matter abnormalities (11/15, 73%), and ventriculomegaly (5/15, 33%). CONCLUSIONS: Abnormal findings in neuroimaging studies are frequent in MPS (dilated Virchow-Robin perivascular spaces, white matter abnormalities and ventriculomegaly). Thus, given these abnormalities we should be aware of this possible diagnosis, particularly when typical signs and symptoms are present. However, we did not find a correlation between these findings and either any specific type of MPS or clinical severity. (+info)