Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct <i>GLB1</i>-Related Dysostosis Multiplex
Morquio B disease (MBD) is an autosomal recessive <i>GLB1</i>-gene-related lysosomal storage disease, presenting with a peculiar type of dysostosis multiplex which is also observed in <i>GALNS</i>-related Morquio A disease. MBD may present as pure skeletal phenotype (<i>...
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9121 |
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| author | Nataliya Yuskiv Katsumi Higaki Sylvia Stockler-Ipsiroglu |
| author_facet | Nataliya Yuskiv Katsumi Higaki Sylvia Stockler-Ipsiroglu |
| author_sort | Nataliya Yuskiv |
| collection | DOAJ |
| description | Morquio B disease (MBD) is an autosomal recessive <i>GLB1</i>-gene-related lysosomal storage disease, presenting with a peculiar type of dysostosis multiplex which is also observed in <i>GALNS</i>-related Morquio A disease. MBD may present as pure skeletal phenotype (<i>pure MBD</i>) or in combination with the neuronopathic manifestations seen in type 2 (juvenile) or type 3 (late onset) GM1 gangliosidosis (<i>MBD plus</i>). 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 <i>GLB1</i> variants in MBD, W273L being invariably associated with <i>pure MBD</i>. 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. |
| first_indexed | 2024-03-10T14:25:46Z |
| format | Article |
| id | doaj.art-f0644c62cdbb4289ab8468c5518e077b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:25:46Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f0644c62cdbb4289ab8468c5518e077b2023-11-20T23:00:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123912110.3390/ijms21239121Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct <i>GLB1</i>-Related Dysostosis MultiplexNataliya Yuskiv0Katsumi Higaki1Sylvia Stockler-Ipsiroglu2BC Children’s Hospital, University of British Columbia, Vancouver, BC V6H 3V4, CanadaResearch Initiative Center, Organization for Research Initiative and Promotion, Tottori University, Yonago 683-8503, JapanBC Children’s Hospital, University of British Columbia, Vancouver, BC V6H 3V4, CanadaMorquio B disease (MBD) is an autosomal recessive <i>GLB1</i>-gene-related lysosomal storage disease, presenting with a peculiar type of dysostosis multiplex which is also observed in <i>GALNS</i>-related Morquio A disease. MBD may present as pure skeletal phenotype (<i>pure MBD</i>) or in combination with the neuronopathic manifestations seen in type 2 (juvenile) or type 3 (late onset) GM1 gangliosidosis (<i>MBD plus</i>). 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 <i>GLB1</i> variants in MBD, W273L being invariably associated with <i>pure MBD</i>. 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.https://www.mdpi.com/1422-0067/21/23/9121Mucopolysaccharidosis type 4MPS4BGM1 gangliosidosisbeta-galactosidase<i>GLB1</i>keratan sulfate |
| spellingShingle | Nataliya Yuskiv Katsumi Higaki Sylvia Stockler-Ipsiroglu Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct <i>GLB1</i>-Related Dysostosis Multiplex International Journal of Molecular Sciences Mucopolysaccharidosis type 4 MPS4B GM1 gangliosidosis beta-galactosidase <i>GLB1</i> keratan sulfate |
| title | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct <i>GLB1</i>-Related Dysostosis Multiplex |
| title_full | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct <i>GLB1</i>-Related Dysostosis Multiplex |
| title_fullStr | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct <i>GLB1</i>-Related Dysostosis Multiplex |
| title_full_unstemmed | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct <i>GLB1</i>-Related Dysostosis Multiplex |
| title_short | Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct <i>GLB1</i>-Related Dysostosis Multiplex |
| title_sort | morquio b disease disease characteristics and treatment options of a distinct i glb1 i related dysostosis multiplex |
| topic | Mucopolysaccharidosis type 4 MPS4B GM1 gangliosidosis beta-galactosidase <i>GLB1</i> keratan sulfate |
| url | https://www.mdpi.com/1422-0067/21/23/9121 |
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