Mucopolysacccharidoses: from understanding to treatment, a century of discoveries

Detalhes bibliográficos
Autor(a) principal: Giugliani,Roberto
Data de Publicação: 2012
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Genetics and Molecular Biology
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572012000600006
Resumo: After the first description of a patient recognized as a MPS case was made in 1917, several similar cases were described and identified. Observations reported in the middle of the twentieth century concerning the presence of acid mucopolysaccharides (later called glycosaminoglycans, or GAGs) in tissues and especially in urine of patients were instrumental in providing an identity for these diseases, which became referred as "mucopolysaccharidoses" (MPS). In the late 1960's it was demonstrated that MPS were caused by defects in the breakdown of GAGs, and the specific enzyme deficiencies for the 11 types and subtypes of MPS were identified thereafter. Genes involved in the MPS were subsequently identified, and a large number of disease-causing mutations were identified in each one. Although individually rare, MPS are relatively frequent as a group, with an overall incidence estimated as 1:22,000. The increased excretion of urinary GAGs observed in the vast majority of MPS patients provides a simple screening method, the diagnosis usually being confirmed by the identification of the specific enzyme deficiency. Molecular analysis also plays a role, being helpful for phenotype prediction, prenatal diagnosis and especially for the identification of carriers. As the diseases are rare and diagnosis requires sophisticated methods, the establishment of reference laboratories for MPS identification is recommended. The successful experience of the MPS Brazil Network in providing access to information and diagnosis may be considered as an option for developing countries. The development of therapeutic strategies for MPS, including bone marrow/hematopoietic stem cell transplantation (BMT/HSCT) and enzyme replacement therapy (ERT), changed the natural history of many MPS types. However, some challenges still remain, including the prevention of cognitive decline which occurs in some MPS. Newer approaches, such as intratechal ERT, substrate reduction therapy, read-through, gene therapy and encapsulated modified cells may provide a better outcome for these diseases in the near future. As early diagnosis and early treatment seems to improve treatment outcomes, and as newborn screening is now technically feasible, pilot programs (including one in progress in an area with high-incidence of MPS VI in northeastern Brazil) should provide information about its potential impact in reducing the morbidity associated with MPS diseases.
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spelling Mucopolysacccharidoses: from understanding to treatment, a century of discoveriesmucopoloysaccharidoseslysosomal diseasesenzyme replacement therapyprenatal diagnosisnewborn screeningAfter the first description of a patient recognized as a MPS case was made in 1917, several similar cases were described and identified. Observations reported in the middle of the twentieth century concerning the presence of acid mucopolysaccharides (later called glycosaminoglycans, or GAGs) in tissues and especially in urine of patients were instrumental in providing an identity for these diseases, which became referred as "mucopolysaccharidoses" (MPS). In the late 1960's it was demonstrated that MPS were caused by defects in the breakdown of GAGs, and the specific enzyme deficiencies for the 11 types and subtypes of MPS were identified thereafter. Genes involved in the MPS were subsequently identified, and a large number of disease-causing mutations were identified in each one. Although individually rare, MPS are relatively frequent as a group, with an overall incidence estimated as 1:22,000. The increased excretion of urinary GAGs observed in the vast majority of MPS patients provides a simple screening method, the diagnosis usually being confirmed by the identification of the specific enzyme deficiency. Molecular analysis also plays a role, being helpful for phenotype prediction, prenatal diagnosis and especially for the identification of carriers. As the diseases are rare and diagnosis requires sophisticated methods, the establishment of reference laboratories for MPS identification is recommended. The successful experience of the MPS Brazil Network in providing access to information and diagnosis may be considered as an option for developing countries. The development of therapeutic strategies for MPS, including bone marrow/hematopoietic stem cell transplantation (BMT/HSCT) and enzyme replacement therapy (ERT), changed the natural history of many MPS types. However, some challenges still remain, including the prevention of cognitive decline which occurs in some MPS. Newer approaches, such as intratechal ERT, substrate reduction therapy, read-through, gene therapy and encapsulated modified cells may provide a better outcome for these diseases in the near future. As early diagnosis and early treatment seems to improve treatment outcomes, and as newborn screening is now technically feasible, pilot programs (including one in progress in an area with high-incidence of MPS VI in northeastern Brazil) should provide information about its potential impact in reducing the morbidity associated with MPS diseases.Sociedade Brasileira de Genética2012-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572012000600006Genetics and Molecular Biology v.35 n.4 suppl.1 2012reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/S1415-47572012000600006info:eu-repo/semantics/openAccessGiugliani,Robertoeng2012-12-18T00:00:00Zoai:scielo:S1415-47572012000600006Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2012-12-18T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false
dc.title.none.fl_str_mv Mucopolysacccharidoses: from understanding to treatment, a century of discoveries
title Mucopolysacccharidoses: from understanding to treatment, a century of discoveries
spellingShingle Mucopolysacccharidoses: from understanding to treatment, a century of discoveries
Giugliani,Roberto
mucopoloysaccharidoses
lysosomal diseases
enzyme replacement therapy
prenatal diagnosis
newborn screening
title_short Mucopolysacccharidoses: from understanding to treatment, a century of discoveries
title_full Mucopolysacccharidoses: from understanding to treatment, a century of discoveries
title_fullStr Mucopolysacccharidoses: from understanding to treatment, a century of discoveries
title_full_unstemmed Mucopolysacccharidoses: from understanding to treatment, a century of discoveries
title_sort Mucopolysacccharidoses: from understanding to treatment, a century of discoveries
author Giugliani,Roberto
author_facet Giugliani,Roberto
author_role author
dc.contributor.author.fl_str_mv Giugliani,Roberto
dc.subject.por.fl_str_mv mucopoloysaccharidoses
lysosomal diseases
enzyme replacement therapy
prenatal diagnosis
newborn screening
topic mucopoloysaccharidoses
lysosomal diseases
enzyme replacement therapy
prenatal diagnosis
newborn screening
description After the first description of a patient recognized as a MPS case was made in 1917, several similar cases were described and identified. Observations reported in the middle of the twentieth century concerning the presence of acid mucopolysaccharides (later called glycosaminoglycans, or GAGs) in tissues and especially in urine of patients were instrumental in providing an identity for these diseases, which became referred as "mucopolysaccharidoses" (MPS). In the late 1960's it was demonstrated that MPS were caused by defects in the breakdown of GAGs, and the specific enzyme deficiencies for the 11 types and subtypes of MPS were identified thereafter. Genes involved in the MPS were subsequently identified, and a large number of disease-causing mutations were identified in each one. Although individually rare, MPS are relatively frequent as a group, with an overall incidence estimated as 1:22,000. The increased excretion of urinary GAGs observed in the vast majority of MPS patients provides a simple screening method, the diagnosis usually being confirmed by the identification of the specific enzyme deficiency. Molecular analysis also plays a role, being helpful for phenotype prediction, prenatal diagnosis and especially for the identification of carriers. As the diseases are rare and diagnosis requires sophisticated methods, the establishment of reference laboratories for MPS identification is recommended. The successful experience of the MPS Brazil Network in providing access to information and diagnosis may be considered as an option for developing countries. The development of therapeutic strategies for MPS, including bone marrow/hematopoietic stem cell transplantation (BMT/HSCT) and enzyme replacement therapy (ERT), changed the natural history of many MPS types. However, some challenges still remain, including the prevention of cognitive decline which occurs in some MPS. Newer approaches, such as intratechal ERT, substrate reduction therapy, read-through, gene therapy and encapsulated modified cells may provide a better outcome for these diseases in the near future. As early diagnosis and early treatment seems to improve treatment outcomes, and as newborn screening is now technically feasible, pilot programs (including one in progress in an area with high-incidence of MPS VI in northeastern Brazil) should provide information about its potential impact in reducing the morbidity associated with MPS diseases.
publishDate 2012
dc.date.none.fl_str_mv 2012-01-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572012000600006
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dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S1415-47572012000600006
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Genética
publisher.none.fl_str_mv Sociedade Brasileira de Genética
dc.source.none.fl_str_mv Genetics and Molecular Biology v.35 n.4 suppl.1 2012
reponame:Genetics and Molecular Biology
instname:Sociedade Brasileira de Genética (SBG)
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instname_str Sociedade Brasileira de Genética (SBG)
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reponame_str Genetics and Molecular Biology
collection Genetics and Molecular Biology
repository.name.fl_str_mv Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)
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