Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy
A significant proportion of adult-onset neurological disorders remain diagnostic odysseys despite extensive evaluation. Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity (HBSL) is an autosomal recessive disorder caused by mutations in the cytoplasmic aspartyl-tRNA synthet...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/169690 |
| _version_ | 1826123649759838208 |
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| author | Tan, Ai Huey Ng, Adeline Su Lyn Ramli, Norlisah Mohd Lim, Weng Khong Cheah, Peng Loon Teo, Jing Xian Kuan, Jyn Ling Tan, Yi Jayne Lim, Jia Lun Chew, Elaine Guo Yan Foo, Jia Nee Goh, Khean Jin Tan, Eng-King Lim, Shen-Yang |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Tan, Ai Huey Ng, Adeline Su Lyn Ramli, Norlisah Mohd Lim, Weng Khong Cheah, Peng Loon Teo, Jing Xian Kuan, Jyn Ling Tan, Yi Jayne Lim, Jia Lun Chew, Elaine Guo Yan Foo, Jia Nee Goh, Khean Jin Tan, Eng-King Lim, Shen-Yang |
| author_sort | Tan, Ai Huey |
| collection | NTU |
| description | A significant proportion of adult-onset neurological disorders remain diagnostic odysseys despite extensive evaluation. Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity (HBSL) is an autosomal recessive disorder caused by mutations in the cytoplasmic aspartyl-tRNA synthetase (DARS) gene involved in mRNA translation. Clinical features of patients with DARS mutations include developmental delay, leg spasticity, cerebellar dysfunction, cognitive impairment and epilepsy. Most reported cases have been infantile-onset with severe neurological disability and neuroimaging abnormalities. To our knowledge, late-or adult-onset cases have never been reported in the literature. Here, we report for the first time, with video documentation and six-year clinical follow-up, an ethnic Malay patient with onset of spasticity and ataxia in late-adulthood, carrying a pathogenic DARS mutation discovered via whole-genome sequencing. His clinical and radiological findings were consistent with HBSL, but this diagnosis was not considered as, up until now, HBSL has only been reported with childhood/adolescent-onset. This case highlights that HBSL/DARS mutations should now be considered in the differential diagnosis of adult-onset spastic paraplegia and/or leukoencephalopathy. |
| first_indexed | 2024-10-01T06:07:48Z |
| format | Journal Article |
| id | ntu-10356/169690 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:07:48Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1696902023-08-06T15:38:05Z Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy Tan, Ai Huey Ng, Adeline Su Lyn Ramli, Norlisah Mohd Lim, Weng Khong Cheah, Peng Loon Teo, Jing Xian Kuan, Jyn Ling Tan, Yi Jayne Lim, Jia Lun Chew, Elaine Guo Yan Foo, Jia Nee Goh, Khean Jin Tan, Eng-King Lim, Shen-Yang Lee Kong Chian School of Medicine (LKCMedicine) Genome Institute of Singapore, A*STAR Science::Medicine Spastic Paraplegia Leukoencephalopathy A significant proportion of adult-onset neurological disorders remain diagnostic odysseys despite extensive evaluation. Hypomyelination with Brainstem and Spinal Cord Involvement and Leg Spasticity (HBSL) is an autosomal recessive disorder caused by mutations in the cytoplasmic aspartyl-tRNA synthetase (DARS) gene involved in mRNA translation. Clinical features of patients with DARS mutations include developmental delay, leg spasticity, cerebellar dysfunction, cognitive impairment and epilepsy. Most reported cases have been infantile-onset with severe neurological disability and neuroimaging abnormalities. To our knowledge, late-or adult-onset cases have never been reported in the literature. Here, we report for the first time, with video documentation and six-year clinical follow-up, an ethnic Malay patient with onset of spasticity and ataxia in late-adulthood, carrying a pathogenic DARS mutation discovered via whole-genome sequencing. His clinical and radiological findings were consistent with HBSL, but this diagnosis was not considered as, up until now, HBSL has only been reported with childhood/adolescent-onset. This case highlights that HBSL/DARS mutations should now be considered in the differential diagnosis of adult-onset spastic paraplegia and/or leukoencephalopathy. National Research Foundation (NRF) Published version This study was funded by Singapore’s SingHealth Foundation (SHF) Institute of Precision Medicine (PRISM) Research Grant (SHF/PRISM008/2016), Singapore’s National Research Foundation (NRF) Fellowship (NRF-NRFF2016-03), and the University of Malaya Parkinson’s Disease and Movement Disorder Research Program (PV035-2017). 2023-07-31T05:21:10Z 2023-07-31T05:21:10Z 2023 Journal Article Tan, A. H., Ng, A. S. L., Ramli, N. M., Lim, W. K., Cheah, P. L., Teo, J. X., Kuan, J. L., Tan, Y. J., Lim, J. L., Chew, E. G. Y., Foo, J. N., Goh, K. J., Tan, E. & Lim, S. (2023). Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy. Neurology Asia, 28(1), 185-189. https://dx.doi.org/10.54029/2023vkd 1823-6138 https://hdl.handle.net/10356/169690 10.54029/2023vkd 2-s2.0-85153492347 1 28 185 189 en SHF/PRISM008/2016 NRF-NRFF2016-03 Neurology Asia © Neurology Asia. Published by ASEAN Neurological Association. This is an open-access article distributed under the terms of the Creative Commons Attribution License. application/pdf |
| spellingShingle | Science::Medicine Spastic Paraplegia Leukoencephalopathy Tan, Ai Huey Ng, Adeline Su Lyn Ramli, Norlisah Mohd Lim, Weng Khong Cheah, Peng Loon Teo, Jing Xian Kuan, Jyn Ling Tan, Yi Jayne Lim, Jia Lun Chew, Elaine Guo Yan Foo, Jia Nee Goh, Khean Jin Tan, Eng-King Lim, Shen-Yang Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy |
| title | Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy |
| title_full | Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy |
| title_fullStr | Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy |
| title_full_unstemmed | Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy |
| title_short | Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy |
| title_sort | expanding the dars phenotype late adult onset myelopathy and leukoencephalopathy |
| topic | Science::Medicine Spastic Paraplegia Leukoencephalopathy |
| url | https://hdl.handle.net/10356/169690 |
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