Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotype
Abstract Background Morquio B disease (MBD) is a distinct GLB1‐related dysostosis multiplex presenting a mild phenocopy of GALNS‐related Morquio A disease. Previously reported cases from European countries carry the W273L variant on at least one GLB1 allele and exhibit a pure skeletal phenotype (pur...
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12211 |
| _version_ | 1818437860885266432 |
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| author | Sylvia Stockler‐Ipsiroglu Nahid Yazdanpanah Mojgan Yazdanpanah Marioara Moisa Popurs Nataliya Yuskiv Mara Lúcia Schmitz Ferreira Santos Chong Ae Kim Carolina Fischinger Moura de Souza Charles Marques Lourenço Carlos Eduardo Steiner Andressa Federhen Luciana Giugliani Débora Maria Bastos Pereira Luz Elena Durán‐Carabali Roberto Giugliani |
| author_facet | Sylvia Stockler‐Ipsiroglu Nahid Yazdanpanah Mojgan Yazdanpanah Marioara Moisa Popurs Nataliya Yuskiv Mara Lúcia Schmitz Ferreira Santos Chong Ae Kim Carolina Fischinger Moura de Souza Charles Marques Lourenço Carlos Eduardo Steiner Andressa Federhen Luciana Giugliani Débora Maria Bastos Pereira Luz Elena Durán‐Carabali Roberto Giugliani |
| author_sort | Sylvia Stockler‐Ipsiroglu |
| collection | DOAJ |
| description | Abstract Background Morquio B disease (MBD) is a distinct GLB1‐related dysostosis multiplex presenting a mild phenocopy of GALNS‐related Morquio A disease. Previously reported cases from European countries carry the W273L variant on at least one GLB1 allele and exhibit a pure skeletal phenotype (pure MBD). Only a minority of MBD cases have been described with additional neuronopathic findings (MBD plus). Objectives and Methods With the aim to further describe patterns of MBD‐related dysostosis multiplex, we analyzed clinical, biochemical, and genetic features in 17 cases with GLB1‐related dysostosis multiplex living and diagnosed in Brazil. Results About 14 of the 17 individuals had three or more skeletal findings characteristic of Morquio syndrome. Two had no additional neuronopathic features (pure MBD) and 12 exhibited additional neuronopathic features (MBD plus). Three of the 17 cases had mild dysostosis without distinct features of MBD. Seven of the 12 MBD plus patients had signs of spinal cord compression (SCC), as a result of progressive spinal vertebral dysostosis. There was an age‐dependent increase in the number of skeletal findings and in the severity of growth impairment. GLB1 mutation analysis was completed in 10 of the 14 MBD patients. T500A occurred in compound heterozygosity in 8 of the 19 alleles. Conclusion Our study extends the phenotypic spectrum of GLB1‐related conditions by describing a cohort of patients with MBD and GM1‐gangliosidosis (MBD plus). Targeting the progressive nature of the skeletal manifestations in the development of new therapies for GLB1‐related conditions is warranted. |
| first_indexed | 2024-12-14T17:31:23Z |
| format | Article |
| id | doaj.art-5f21718127ef4c69b7006f56d0a4bbcc |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-12-14T17:31:23Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-5f21718127ef4c69b7006f56d0a4bbcc2022-12-21T22:53:05ZengWileyJIMD Reports2192-83122021-07-01601233110.1002/jmd2.12211Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotypeSylvia Stockler‐Ipsiroglu0Nahid Yazdanpanah1Mojgan Yazdanpanah2Marioara Moisa Popurs3Nataliya Yuskiv4Mara Lúcia Schmitz Ferreira Santos5Chong Ae Kim6Carolina Fischinger Moura de Souza7Charles Marques Lourenço8Carlos Eduardo Steiner9Andressa Federhen10Luciana Giugliani11Débora Maria Bastos Pereira12Luz Elena Durán‐Carabali13Roberto Giugliani14Department of Pediatrics University of British Columbia Vancouver CanadaDepartment of Pediatrics University of British Columbia Vancouver CanadaDepartment of Pediatrics University of British Columbia Vancouver CanadaDepartment of Pediatrics University of British Columbia Vancouver CanadaDepartment of Pediatrics University of British Columbia Vancouver CanadaHospital Infantil Pequeno Príncipe Curitiba BrazilInstituto da Criança, Faculdade de Medicina, USP São Paulo BrazilServiço de Genética Médica, HCPA Porto Alegre BrazilFaculdade de Medicina Centro Universitário Estácio Ribeirão Preto BrazilDepartamento de Genética Médica, Faculdade de Medicina UNICAMP Campinas BrazilServiço de Genética Médica, HCPA Porto Alegre BrazilServiço de Genética Médica, HCPA Porto Alegre BrazilServiço de Genética Médica, HCPA Porto Alegre BrazilPrograma de Pós‐Graduação em Ciências Biológicas: Fisiologia, UFRGS Porto Alegre BrazilServiço de Genética Médica, HCPA Porto Alegre BrazilAbstract Background Morquio B disease (MBD) is a distinct GLB1‐related dysostosis multiplex presenting a mild phenocopy of GALNS‐related Morquio A disease. Previously reported cases from European countries carry the W273L variant on at least one GLB1 allele and exhibit a pure skeletal phenotype (pure MBD). Only a minority of MBD cases have been described with additional neuronopathic findings (MBD plus). Objectives and Methods With the aim to further describe patterns of MBD‐related dysostosis multiplex, we analyzed clinical, biochemical, and genetic features in 17 cases with GLB1‐related dysostosis multiplex living and diagnosed in Brazil. Results About 14 of the 17 individuals had three or more skeletal findings characteristic of Morquio syndrome. Two had no additional neuronopathic features (pure MBD) and 12 exhibited additional neuronopathic features (MBD plus). Three of the 17 cases had mild dysostosis without distinct features of MBD. Seven of the 12 MBD plus patients had signs of spinal cord compression (SCC), as a result of progressive spinal vertebral dysostosis. There was an age‐dependent increase in the number of skeletal findings and in the severity of growth impairment. GLB1 mutation analysis was completed in 10 of the 14 MBD patients. T500A occurred in compound heterozygosity in 8 of the 19 alleles. Conclusion Our study extends the phenotypic spectrum of GLB1‐related conditions by describing a cohort of patients with MBD and GM1‐gangliosidosis (MBD plus). Targeting the progressive nature of the skeletal manifestations in the development of new therapies for GLB1‐related conditions is warranted.https://doi.org/10.1002/jmd2.12211dystoniakeratan sulfatemucopolysaccharidosis type IVBspondyloepiphyseal dysplasiatype 3 GM1 gangliosidosisβ‐galactosidase |
| spellingShingle | Sylvia Stockler‐Ipsiroglu Nahid Yazdanpanah Mojgan Yazdanpanah Marioara Moisa Popurs Nataliya Yuskiv Mara Lúcia Schmitz Ferreira Santos Chong Ae Kim Carolina Fischinger Moura de Souza Charles Marques Lourenço Carlos Eduardo Steiner Andressa Federhen Luciana Giugliani Débora Maria Bastos Pereira Luz Elena Durán‐Carabali Roberto Giugliani Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotype JIMD Reports dystonia keratan sulfate mucopolysaccharidosis type IVB spondyloepiphyseal dysplasia type 3 GM1 gangliosidosis β‐galactosidase |
| title | Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotype |
| title_full | Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotype |
| title_fullStr | Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotype |
| title_full_unstemmed | Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotype |
| title_short | Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotype |
| title_sort | morquio like dysostosis multiplex presenting with neuronopathic features is a distinct glb1 related phenotype |
| topic | dystonia keratan sulfate mucopolysaccharidosis type IVB spondyloepiphyseal dysplasia type 3 GM1 gangliosidosis β‐galactosidase |
| url | https://doi.org/10.1002/jmd2.12211 |
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