The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I

Broomfield, Alexander; Sims, Jason; Mercer, Jean; Hensman, Pauline; Ghosh, Arunabha; Tylee, Karen; Stępień, Karolina M.; Oldham, Andrew; Bhayankaram, N Prathivadi; Wynn, Robert; Wright, Neville; Jones, Simon A.; Wilkinson, Stuart

doi:10.1016/j.ymgme.2020.07.004

Cited by 6 publications

(6 citation statements)

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“…A large retrospective study of patients treated with ERT and/or HSCT showed improvement or stabilization of pulmonary function in the majority of patients for the duration of over 12 years. However, residual restrictive lung disease remained in all patients and 1/3 of the patients experienced progressive loss of pulmonary function despite treatment [ 111 ]. Other studies reported ongoing overnight hypoxia, suggesting incomplete resolution of pulmonary insufficiency [ 29 ].…”

Section: Impact Of Hsct and Ert On Tissue-specific Disease Manifesmentioning

confidence: 99%

Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement

et al. 2021

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Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the glycosaminoglycans dermatan and heparan sulfate (DS and HS, respectively). Lack of the enzyme leads to pathologic accumulation of undegraded HS and DS with subsequent disease manifestations in multiple organs. The disease can be divided into severe (Hurler syndrome) and attenuated (Hurler-Scheie, Scheie) forms. Currently approved treatments consist of enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). Patients with attenuated disease are often treated with ERT alone, while the recommended therapy for patients with Hurler syndrome consists of HSCT. While these treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains. Notably, treatment can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment. This review discusses these standard therapies and their impact on common disease manifestations in patients with MPS I. Where relevant, results of animal models of MPS I will be included. Finally, we highlight alternative and emerging treatments for the most common disease manifestations.

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Section: Impact Of Hsct and Ert On Tissue-specific Disease Manifesmentioning

confidence: 99%

Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement

et al. 2021

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“…IDS is administered weekly at 0.5 mg/kg as an intravenous infusion. ERT has significantly lowered the risk of death in patients with MPS II [31,[191][192][193] and has had a beneficial effect on many of the biochemical and systemic manifestations, including reduced urinary GAG excretion levels, decreased volumes of liver and spleen, and increased cardiopulmonary function and average walking distance (Table 4) [194,195]. However, it is believed that the enzyme does not cross the blood-brain barrier (BBB) and is, therefore, not likely to have an effect on CNS disease among severely affected patients [196][197][198].…”

Section: Treatmentmentioning

confidence: 99%

Differences in MPS I and MPS II Disease Manifestations

Hampe

Yund

Orchard

et al. 2021

IJMS

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Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation. Characteristic phenotypical manifestations of both MPS I and II include skeletal disease, reflected in short stature, inguinal and umbilical hernias, hydrocephalus, hearing loss, coarse facial features, protruded abdomen with hepatosplenomegaly, and neurological involvement with varying functional concerns. However, a few manifestations are disease-specific, including corneal clouding in MPS I, epidermal manifestations in MPS II, and differences in the severity and nature of behavioral concerns. These phenotypic differences appear to be related to different ratios between DS and HS, and their sulfation levels. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while HS levels dominate over DS levels in MPS II and sulfation levels are higher. The high presence of DS in the cornea and its involvement in the arrangement of collagen fibrils potentially causes corneal clouding to be prevalent in MPS I, but not in MPS II. The differences in neurological involvement may be due to the increased HS levels in MPS II, because of the involvement of HS in neuronal development. Current treatment options for patients with MPS II are often restricted to enzyme replacement therapy (ERT). While ERT has beneficial effects on respiratory and cardiopulmonary function and extends the lifespan of the patients, it does not significantly affect CNS manifestations, probably because the enzyme cannot pass the blood–brain barrier at sufficient levels. Many experimental therapies, therefore, aim at delivery of IDS to the CNS in an attempt to prevent neurocognitive decline in the patients.

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“…Respecto a las alteraciones del fuelle torácico, estas se manifiestan en aquellas MPS con compromiso esquelético más grave (tipos I, II, IV y VI) y se caracterizan por deformidades y rigidez de las articulaciones costales, horizontalización de las costillas, escoliosis, cifosis, xifoescoliosis y pectus carinatum. También la hepatoesplenomegalia grave se asocia con estas malformaciones, provocando una mayor reducción de la capacidad vital 16,17 y manifestando una enfermedad pulmonar restrictiva de diversos grados 18 .…”

Section: Características Anatomofisiopatológicas De Los Pacientes Con Mucopolisacaridosisunclassified

“…El objetivo de la fisioterapia respiratoria es mejorar la alteración restrictiva pulmonar en la MPS, la cual es el resultado de la obstrucción provocada en la vía aérea superior, el acortamiento muscular respiratorio, la deformidad del tórax y de la columna dorsal, la hepatomegalia y la broncoaspiración causada por la disfagia 41 . Estos mecanismos llevarán a una reducción en la expansión y la movilidad torácica, y a la producción de tos ineficaz que se traducirá en hipersecreción, infecciones recurrentes y apneas del sueño [16][17][18]43 . Las guías de práctica clínica para el cuidado respiratorio de los pacientes con MPS o enfermedad de Pompe recomiendan iniciar los cuidados respiratorios tempranamente y realizarlos de una a cuatro veces al día 46 .…”

Section: Técnicas De Fisioterapia Respiratoriaunclassified

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Aspectos respiratorios y de fisioterapia pulmonar en el niño con mucopolisacaridosis

Cruz-Anleu¹,

Solís-Trujeque²,

Peña-Hernández³

2021

BMHIM

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La mucopolisacaridosis es un grupo heterogéneo de enfermedades que se caracterizan por la acumulación lisosomal de sustancias intermedias del metabolismo de los mucopolisacáridos o glucosaminoglucanos. El trastorno respiratorio que caracteriza a los pacientes con mucopolisacaridosis es la enfermedad pulmonar restrictiva crónica, por lo que la rehabilitación pulmonar, cuyo objetivo es mejorar los síntomas respiratorios, y la fisioterapia respiratoria, mejorarán la ventilación pulmonar y la biomecánica respiratoria deteriorada. Es necesario el seguimiento por el neumólogo infantil, quien cuantificará la función pulmonar y vigilará los síntomas de obstrucción nocturna y de restricción pulmonar con ayuda de estudios como la espirometría, la pletismografía y la prueba de la caminata de 6 minutos, por mencionar algunas. También es muy importante realizar un programa individualizado de técnicas de fisioterapia respiratoria y de ejercicios. Todo lo anterior, con el objetivo de evaluar la función pulmonar como un marcador de respuesta al uso de cualquiera de las terapias indicadas en la mucopolisacaridosis.

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The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I

Cited by 6 publications

References 30 publications

Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement

Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement

Differences in MPS I and MPS II Disease Manifestations

Aspectos respiratorios y de fisioterapia pulmonar en el niño con mucopolisacaridosis

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