Low β-glucuronidase enzyme activity and mutations in the human β-glucuronidase gene in mild mucopolysaccharidosis type VII, pseudodeficiency and a heterozygote

Vervoort, Raf; Gitzelmann, R; Bosshard, Nils U.; Maire, I.; Liebaers, Inge; Lissens, Willy

doi:10.1007/s004390050656

Cited by 29 publications

(21 citation statements)

References 36 publications

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“…Some MPS VII patients with less severe clinical phenotypes than our treated mice have comparable enzyme levels (Vervoort et al 1998). However, these patients likely express this level of activity in every cell, making them fundamentally different from our mice, whose cells endocytose GUSB from an external source.…”

Section: Discussionmentioning

confidence: 96%

Clinical response to persistent, low‐level β‐glucuronidase expression in the murine model of mucopolysaccharidosis type VII

Donsante¹,

Levy

Vogler

et al. 2007

J of Inher Metab Disea

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Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by beta-glucuronidase (GUSB) deficiency. This disease exhibits a broad spectrum of clinical signs including skeletal dysplasia, retinal degeneration, cognitive deficits and hearing impairment. Sustained, high-level expression of GUSB significantly improves the clinical course of the disease in the murine model of MPS VII. Low levels of enzyme expression (1-5% of normal) can significantly reduce the biochemical and histopathological manifestations of MPS VII. However, it has not been clear from previous studies whether persistent, low levels of circulating GUSB lead to significant improvements in the clinical presentation of this disease. We generated a rAAV2 vector that mediates persistent, low-level GUSB expression in the liver. Liver and serum levels of GUSB were maintained at approximately 5% and approximately 2.5% of normal, respectively, while other tissue ranged from background levels to 0.9%. This level of activity significantly reduced the secondary elevations of alpha-galactosidase and the levels of glycosaminoglycans in multiple tissues. Interestingly, this level of GUSB was also sufficient to reduce lysosomal storage in neurons in the brain. Although there were small but statistically significant improvements in retinal function, auditory function, skeletal dysplasia, and reproduction in rAAV-treated MPS VII mice, the clinical deficits were still profound and there was no improvement in lifespan. These data suggest that circulating levels of GUSB greater than 2.5% will be required to achieve substantial clinical improvements in MPS VII.

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Section: Discussionmentioning

confidence: 96%

Clinical response to persistent, low‐level β‐glucuronidase expression in the murine model of mucopolysaccharidosis type VII

Donsante¹,

Levy

Vogler

et al. 2007

J of Inher Metab Disea

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“…However, there have also been reports of patients with β-glucuronidase deficiency who show extremely mild MPS as features (Vervoort et al 1998). Because of this remarkable clinical variability, mucopolysaccharidosis type VII is probably underdiagnosed.…”

Section: Discussionmentioning

confidence: 97%

Cumulative incidence rates of the mucopolysaccharidoses in Germany

Baehner

Schmiedeskamp

Krummenauer³

et al. 2005

J of Inher Metab Disea

354

251

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In order to estimate the cumulative incidence rates of the mucopolysaccharidoses (MPS) in Germany, a retrospective epidemiological survey covering the period between 1980 and 1995 was implemented. Multiple ascertainment sources were used to identify affected patients. A prevalence of approximately 0.69 cases per 100,000 births was obtained for MPS I (Hurler phenotype). Within the study period, 4 patients with Hurler/Scheie phenotype and 7 cases with Scheie disease were detected. The cumulative incidence for MPS II (Hunter syndrome) was estimated as 0.64 cases per 100,000 births (1.3 cases per 100,000 male live births); that for MPS III (Sanfilippo syndrome types A, B and C) as 1.57 cases in 100,000 births; that for MPS IV A (Morquio syndrome) as 0.38 cases in 100,000; and that for MPS VI (Maroteaux-Lamy syndrome) as 0.23 cases per 100,000 births. Two cases of MPS IVB (beta-galactosidase deficiency) have been identified, but no patients with MPS VII or MPS IX. A relatively high number of patients with MPS IIIB, MPS IVA and MPS VI were of Turkish origin. The crude rate for all types of mucopolysaccharidoses is approximately 3.53 cases in 100,000 live births. The cumulative incidence pattern of MPS in Germany was compared with the corresponding rates among other industrial nations obtained from recent literature: the crude cumulative rates for all types of mucopolysaccharidoses (3.4-4.5 in 100,000 live births) were similar among all published populations; however, different frequencies of the various forms of MPS were observed.

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“…La forma de presentación más común de la mucopolisacaridosis VII es la eritroblastosis fetal (hydrops fetalis) (27). Sin embargo hay algunos reportes de pacientes con esta enfermedad que muestran características extremadamente leves (28). Esta gran heterogeneidad clínica podría causar un subdiagnóstico de este tipo de mucopolisacaridosis, pero, a pesar de esto, los datos parecen concordar en cuanto a que esta es la forma de mucopolisacaridosis Cuadro 4.…”

Section: Mps I Mps Ii Mps Iii Mps Iv Mps Vi Totalunclassified

Estimación de las frecuencias de las mucopolisacaridosis y análisis de agrupamiento espacial en los departamentos de Cundinamarca y Boyacá

2012

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Introducción. Las mucopolisacaridosis son enfermedades poco frecuentes de depósito lisosómico de glucosaminoglucanos, con datos variables sobre su incidencia en diferentes países a nivel mundial. En Latinoamérica hay reportes de frecuencias en Brasil, pero en Colombia la información es escasa. Objetivos. Estimar las frecuencias de las mucopolisacaridosis mediante un estudio retrospectivo en los departamentos de Cundinamarca y Boyacá, y estimar la agregación espacial de los casos en estos mismos departamentos. Materiales y métodos. Se revisaron los registros de pacientes de diferentes instituciones de referencia para enfermedades genéticas, así como los registros de nacimientos vivos entre 1998 y 2007. Con base en ellos, se estimaron las frecuencias para cada tipo de mucopolisacaridosis. Se analizó la agregación espacial de los casos utilizando el programa SaTScan™. Resultados. La frecuencia combinada para todas las mucopolisacaridosis fue de 1,98 casos por 100.000 nacidos vivos. La mayor frecuencia fue para la de tipo IV, con 0,68 casos por 100.000 nacidos vivos, mientras que la III fue la menor, con 0,17 casos. Se encontraron tres posibles áreas de agregación espacial para las mucopolisacaridosis I, III y IV. Conclusión. La frecuencia combinada para todas las mucopolisacaridosis se encuentra dentro de los rangos reportados en la literatura científica, siendo la de tipo IV la más frecuente y la de tipo VII la menos frecuente. Aunque los datos aquí reportados podrían corresponder a un subregistro, dadas las dificultades inherentes a la recolección de la información en nuestro país, consideramos que son un estimativo válido de las frecuencias de estas enfermedades.Palabras clave: mucopolisacaridosis/epidemiología, errores innatos del metabolismo, enfermedades por almacenamiento lisosómico, análisis por conglomerados. doi: http://dx.doi.org/10.7705/biomedica.v32i4.574 Estimation of the mucopolysaccharidoses frequencies and cluster analysis in the Colombian provinces of Cundinamarca and BoyacáIntroduction. Mucopolysaccharidoses are a group of infrequent disorders caused by the lysosomal deposit of glycosaminoglycans. Its incidence is quite variable among thecountries where it has been documented. In Brazil, disorder frequencies have been reported, but in Colombia information on them is scarce. Objectives. The frequency and spatial aggregations of the mucopolysaccharidoses were estimated by a retrospective study in two central Colombian provinces. Materials and methods. The records of patients and live newborns between 1998-2007 were reviewed from several reference institutions for genetic diseases. From these records, the frequencies for each mucopolysaccharidosis were estimated. The spatial aggregation of the cases was analyzed using the SaTScan software. Results. The combined frequency for all the mucopolysaccharidoses was 1.98 cases per 100,000 live newborns. MPS IV had the highest frequency with 0.68 cases per 100,000 live newborns and MPS III showed a lower frequency of 0.17/100,000. Three spatial aggregation a...

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Low β-glucuronidase enzyme activity and mutations in the human β-glucuronidase gene in mild mucopolysaccharidosis type VII, pseudodeficiency and a heterozygote

Cited by 29 publications

References 36 publications

Clinical response to persistent, low‐level β‐glucuronidase expression in the murine model of mucopolysaccharidosis type VII

Clinical response to persistent, low‐level β‐glucuronidase expression in the murine model of mucopolysaccharidosis type VII

Cumulative incidence rates of the mucopolysaccharidoses in Germany

Estimación de las frecuencias de las mucopolisacaridosis y análisis de agrupamiento espacial en los departamentos de Cundinamarca y Boyacá

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