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...

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Main Authors: 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
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/169690
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Spastic Paraplegia
Leukoencephalopathy
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
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.
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
format Article
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
author_sort Tan, Ai Huey
title Expanding the DARS phenotype: late-adult onset myelopathy and leukoencephalopathy
title_short 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_sort expanding the dars phenotype: late-adult onset myelopathy and leukoencephalopathy
publishDate 2023
url https://hdl.handle.net/10356/169690
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