Cardiac Findings After Enzyme Replacement Therapy for Mucopolysaccharidosis Type I

Braunlin, Elizabeth; Berry, James M.; Whitley, Chester B.

doi:10.1016/j.amjcard.2006.02.047

Cited by 104 publications

(88 citation statements)

References 16 publications

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“…For example, aortic insufficiency developed de novo or worsened in 89% of patients at 12 years after performing hematopoietic stem cell transplantation at ~2 years [30] and in 60% of patients at 4-6 years after starting enzyme replacement therapy [31,32]. Although pathological data were not available, progressive fragmentation of the elastic fibers likely contributed to worsening aortic valve function.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

Tittiger

Knutsen

et al. 2008

Molecular Genetics and Metabolism

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Mucopolysaccharidosis I (MPS I), known as Hurler syndrome in the severe form, is a lysosomal storage disease due to -L-iduronidase (IDUA) deficiency. It results in fragmentation of elastin fibers in the aorta and heart valves via mechanisms that are unclear, but may result from the accumulation of the glycosaminoglycans heparan and dermatan sulfate. Elastin fragmentation causes aortic dilatation and valvular insufficiency, which can result in cardiovascular disease. The pathophysiology of aortic disease was evaluated in MPS I mice. MPS I mice have normal elastic fiber structure and aortic compliance at early ages, which suggests that elastin assembly is normal. Elastin fragmentation and aortic dilatation are severe at 6 months, which is temporally associated with marked increases in mRNA and enzyme activity for two elastin-degrading proteins, matrix metalloproteinase-12 (MMP-12) and cathepsin S. Upregulation of these genes likely involves activation of STAT proteins, which may be induced by structural stress to smooth muscle cells from accumulation of glycosaminoglycans in lysosomes. Neonatal intravenous injection of a retroviral vector normalized MMP-12 and cathepsin S mRNA levels and prevented aortic disease. We conclude that aortic dilatation in MPS I mice is likely due to degradation of elastin by MMP-12 and/or cathepsin S. This aspect of disease might be ameliorated by inhibition of the signal transduction pathways that upregulate expression of elastase proteins, or by inhibition of elastase activity. This could result in a treatment for patients with MPS I, and might reduce aortic aneurism formation in other disorders.

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Section: Discussionmentioning

confidence: 99%

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

Tittiger

Knutsen

et al. 2008

Molecular Genetics and Metabolism

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“…O miocárdio geralmente sofre hipertrofia, as válvulas cardíacas ficam espessadas e levam ao regurgitamento ou estenose, assim como, surgem alterações de grandes vasos, na qual a aorta apresenta a túnica íntima acentuadamente espessada e por vezes são vistas células "claras" nas três túnicas, à histopatologia (Wang et al, 2011;Braunlin et al, 2006). No presente estudo notou-se o espessamento acentuado da túnica íntima e presença de aspecto de células "claras" da aorta, que corresponde a células vacuolizadas.…”

Section: Discussionunclassified

Mucopolissacaridose em um cão: relato de caso

Veiga¹,

Oliveira²,

Silva³

et al. 2017

Braz. J. Vet. Med.

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RELATO DE CASOCopyright Veiga et al. Este é um artigo publicado em acesso aberto (Open Access) sob a licença Creative Commons Attribution Non-Commercial, que permite uso, distribuição e reprodução em qualquer meio, sem restrições desde que sem fins comerciais e que o trabalho original seja corretamente citado. Mucopolissacaridose em um cão: relato de caso ResumoA Mucopolissacaridose é uma doença rara, multissistêmica, progressiva e sem tratamento. Os objetivos deste estudo foram descrever os achados clínicos, radiográficos e anátomo-patológicos de um caso de mucopolissacaridose em um cão. Relata-se um caso de um cão, macho, Fox Paulistinha, de quatro meses de idade, oriundo de cruzamento com alto grau de endogamia. O cão apresentava apatia, dificuldades de locomoção, aumento de volume nas articulações, opacidade de córnea e dispneia inspiratória. Ao exame radiográfico observaram-se alterações bilaterais em linhas fiseais de vértebras, rádio e ulna, hepatomegalia e hipoplasia traqueal. Devido à acentuada dificuldade respiratória, o proprietário optou pela eutanásia. À necropsia, observou-se ausência das cartilagens da laringe, cricoide e aritenoide, coração globoso, e fígado e baço moderadamente aumentados. As alterações ósseas incluíram aumento do perímetro do crânio, má formação do esterno e costelas sinuosas. A histopatologia revelou displasia nas cartilagens da epiglote, da traqueia e articulares, nas quais os condrócitos apresentavam-se com citoplasma vacuolizado; havia ainda acentuado espessamento da íntima da aorta. O histórico de cruzamentos com alto grau de endogamia, associado aos achados clínicos, radiográficos e anátomo-patológicos confluem para o diagnóstico de mucopolissacaridose.Palavras-chave: canino, disostose multiplex, enzimas lisossomais. AbstractMucopolysaccharidosis is a rare, multisystemic, progressive disease that has no cure. The objectives of this study were to describe the clinical, radiographic and anatomical and pathological findings of a case of mucopolysaccharidosis in a dog. It reports the case of a male dog of the Fox Paulistinha (Brazilian Terrier) breed, four months of age, derived from cross-breeding with high degree of endogamy. The animal exhibited apathy, walking difficulty, enlarged joints, opacity of the cornea, and inspiratory dyspnea. On X-ray, bilateral changes were observed in the physeal lines of vertebrae, radius and ulna, as well as enlarged liver and tracheal hypoplasia. Due to the accentuated respiratory difficulty, the owner decided to euthanize the dog. Necropsy showed the absence of the larynx, cricoid and arytenoid cartilages, a distended heart, and moderately enlarged liver and spleen. Bone changes included increased cranial perimeter, malformation of the sternum, and twisted ribs. Histopathology revealed dysplasia in the cartilage of the epiglottis, trachea and joints, in which the chondrocytes presented with vacuolated cytoplasm; there was also accentuated thickening of the aortic intima. The history of cross-breeding with a high degree of endogamy, associ...

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“…Although ERT and HSCT are able to mitigate many symptoms of MPS, it is important to emphasize that they are only treatments and not cures. Certain tissues remain resistant to treatment and continue to manifest GAG storage [3,5,6,7]. In addition, with treatment, more MPS patients are now surviving into adulthood and face a different set of potentially life-threatening disease complications.…”

Section: Introductionmentioning

confidence: 99%

Carotid Intima-Media thickness is increased in patients with mucopolysaccharidoses

Wang

Covault

Dauben

et al. 2011

Molecular Genetics and Metabolism

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Cardiac Findings After Enzyme Replacement Therapy for Mucopolysaccharidosis Type I

Cited by 104 publications

References 16 publications

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

Mucopolissacaridose em um cão: relato de caso

Carotid Intima-Media thickness is increased in patients with mucopolysaccharidoses

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