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Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex
Morquio B disease (MBD) is an autosomal recessive GLB1-gene-related lysosomal storage disease, presenting with a peculiar type of dysostosis multiplex which is also observed in GALNS-related Morquio A disease. MBD may present as pure skeletal phenotype (pure MBD) or in combination with the neuronopa...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729736/ https://www.ncbi.nlm.nih.gov/pubmed/33266180 http://dx.doi.org/10.3390/ijms21239121 |
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author | Yuskiv, Nataliya Higaki, Katsumi Stockler-Ipsiroglu, Sylvia |
author_facet | Yuskiv, Nataliya Higaki, Katsumi Stockler-Ipsiroglu, Sylvia |
author_sort | Yuskiv, Nataliya |
collection | PubMed |
description | Morquio B disease (MBD) is an autosomal recessive GLB1-gene-related lysosomal storage disease, presenting with a peculiar type of dysostosis multiplex which is also observed in GALNS-related Morquio A disease. MBD may present as pure skeletal phenotype (pure MBD) or in combination with the neuronopathic manifestations seen in type 2 (juvenile) or type 3 (late onset) GM1 gangliosidosis (MBD plus). The main skeletal features are progressive growth impairment, kyphoscoliosis, coxa/genua valga, joint laxity, platyspondyly and odontoid hypoplasia. The main neuronopathic features are dystonia, ataxia, and intellectual/developmental/speech delay. Spinal cord compression occurs as a complication of spinal dysostosis. Chronic pain is reported, along with mobility issues and challenges with daily living and self-care activities, as the most common health concern. The most commonly reported orthopedic surgeries are hip and knee replacements. Keratan sulphate-derived oligosaccharides are characteristic biomarkers. Residual β-galactosidase activities measured against synthetic substrates do not correlate with the phenotype. W273 L and T500A are the most frequently observed GLB1 variants in MBD, W273L being invariably associated with pure MBD. Cytokines play a role in joint destruction and pain, providing a promising treatment target. In the future, patients may benefit from small molecule therapies, and gene and enzyme replacement therapies, which are currently being developed for GM1 gangliosidosis. |
format | Online Article Text |
id | pubmed-7729736 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77297362020-12-12 Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex Yuskiv, Nataliya Higaki, Katsumi Stockler-Ipsiroglu, Sylvia Int J Mol Sci Review Morquio B disease (MBD) is an autosomal recessive GLB1-gene-related lysosomal storage disease, presenting with a peculiar type of dysostosis multiplex which is also observed in GALNS-related Morquio A disease. MBD may present as pure skeletal phenotype (pure MBD) or in combination with the neuronopathic manifestations seen in type 2 (juvenile) or type 3 (late onset) GM1 gangliosidosis (MBD plus). The main skeletal features are progressive growth impairment, kyphoscoliosis, coxa/genua valga, joint laxity, platyspondyly and odontoid hypoplasia. The main neuronopathic features are dystonia, ataxia, and intellectual/developmental/speech delay. Spinal cord compression occurs as a complication of spinal dysostosis. Chronic pain is reported, along with mobility issues and challenges with daily living and self-care activities, as the most common health concern. The most commonly reported orthopedic surgeries are hip and knee replacements. Keratan sulphate-derived oligosaccharides are characteristic biomarkers. Residual β-galactosidase activities measured against synthetic substrates do not correlate with the phenotype. W273 L and T500A are the most frequently observed GLB1 variants in MBD, W273L being invariably associated with pure MBD. Cytokines play a role in joint destruction and pain, providing a promising treatment target. In the future, patients may benefit from small molecule therapies, and gene and enzyme replacement therapies, which are currently being developed for GM1 gangliosidosis. MDPI 2020-11-30 /pmc/articles/PMC7729736/ /pubmed/33266180 http://dx.doi.org/10.3390/ijms21239121 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Yuskiv, Nataliya Higaki, Katsumi Stockler-Ipsiroglu, Sylvia Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex |
title | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex |
title_full | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex |
title_fullStr | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex |
title_full_unstemmed | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex |
title_short | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex |
title_sort | morquio b disease. disease characteristics and treatment options of a distinct glb1-related dysostosis multiplex |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729736/ https://www.ncbi.nlm.nih.gov/pubmed/33266180 http://dx.doi.org/10.3390/ijms21239121 |
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