Investigating ABCD1 mutations in a Taiwanese cohort with hereditary spastic paraplegia phenotype
Abstract
BACKGROUND Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder caused by mutations in the ABCD1 gene. The clinical manifestations of ALD vary widely with some patients presenting with adrenomyeloneuropathy (AMN) that resembles the phenotype of hereditary spastic paraplegia (HSP). The aim of this study is to investigate the frequency, spectrum, and clinical features of ABCD1 mutations in Taiwanese patients with HSP phenotype. METHODS Mutational analysis of the ABCD1 gene was performed in 230 unrelated Taiwanese patients with clinically suspected HSP by targeted resequencing. Clinical, electrophysiological, and neuroimaging features of the patients carrying an ABCD1 pathogenic mutation were characterized. RESULTS Ten different ABCD1 mutations were identified in eleven patients, including two novel mutations (p.Q177Pfs*17 and p.Y357*) and eight ever reported in ALD cases of other ethnicities. All patients were male and exhibited slowly progressive spastic paraparesis with onset ages ranging from 21 to 50 years. Most of them had additional non-motor symptoms, including autonomic dysfunction in nine patients, sensory deficits in seven, premature baldness in seven, skin hyperpigmentation in five, psychiatric symptoms in one and cerebellar ataxia in one. Seven of the ten patients who ever received nerve conduction studies showed axonal polyneuropathy. Magnetic resonance imaging (MRI) revealed diffuse spinal cord atrophy in seven patients, cerebral white matter hyperintensity in one patient, and cerebellar involvement in one patient. CONCLUSIONS ABCD1 mutations account for 4.8% (11/230) of the cases with HSP phenotype in Taiwan. This study highlights the importance to consider ABCD1 mutations in patients with clinically suspected HSP of unknown genetic causes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594 · see citing works
Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients
Schüle, R., Wiethoff, S., Martus, P., Karle, K. N., Otto, S., Klebe, S., Klimpe, S., Gallenmüller, C., Kurzwelly, D., Henkel, D., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24611 · Cited by 315 · see citing works
The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein
Mosser, J., Lutz, Y., Stoeckel, M. E., Sarde, C. O., Kretz, C., Douar, A. M., Lopez, J., Aubourg, P., & Mandel, J. L. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.2.265 · Cited by 281 · see citing works
Adrenoleukodystrophy—Neuroendocrine pathogenesis and redefinition of natural history
Kemp, S., Huffnagel, I. C., Linthorst, G. E., Wanders, R. J., & Engelen, M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.90 · Cited by 275 · see citing works
X-linked adrenoleukodystrophy in women: A cross-sectional cohort study
Engelen, M., Barbier, M., Dijkstra, I. M. E., Schür, R., de Bie, R. M. A., Verhamme, C., Dijkgraaf, M. G. W., Aubourg, P. A., Wanders, R. J. A., van Geel, B. M., et al. (2014) · Brain · doi:10.1093/brain/awt361 · Cited by 234 · see citing works
Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks
de Souza, P. V. S., Pinto, W. B. V. D. R., Batistella, G. N. D. R., et al. (2016) · The Cerebellum · doi:10.1007/s12311-016-0803-z · Cited by 214 · see citing works
Adrenomyeloneuropathy: A Neuropathologic Review Featuring Its Noninflammatory Myelopathy
Powers, J. M., DeCiero, D. P., Ito, M., Moser, A. B., & Moser, H. W. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.2.89 · Cited by 204 · see citing works
Advances in the hereditary spastic paraplegias
Fink, J. K. (2003) · Experimental Neurology · doi:10.1016/j.expneurol.2003.08.005 · Cited by 129 · see citing works
Berger, J., Molzer, B., Fae, I., & Bernheimer, H. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2855 · Cited by 126 · see citing works
Galea, E., Launay, N., Portero-Otin, M., Ruiz, M., Pamplona, R., Aubourg, P., Ferrer, I., & Pujol, A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.02.005 · Cited by 108 · see citing works
Mutational analysis of patients with X-linked adrenoleukodystrophy
Kok, F., Neumann, S., Sarde, C.-O., Zheng, S., Wu, K.-H., Wei, H.-M., Bergin, J., Watkins, P. A., Gould, S., Sack, G., et al. (1995) · Human Mutation · doi:10.1002/humu.1380060203 · Cited by 103 · see citing works
Omidvar, M. E., Torkamandi, S., Rezaei, S., et al. (2019) · Journal of Neurology · doi:10.1007/s00415-019-09633-1 · Cited by 92 · see citing works
Neuroimaging in Hereditary Spastic Paraplegias: Current Use and Future Perspectives
da Graça, F. F., de Rezende, T. J. R., Vasconcellos, L. F., et al. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2018.01117 · Cited by 82 · see citing works
Natural history of X-linked adrenoleukodystrophy in Japan
Suzuki, Y., Takemoto, Y., Shimozawa, N., Imanaka, T., Kato, S., Furuya, H., Kaga, M., Kato, K., Hashimoto, N., Onodera, O., et al. (2004) · Brain and Development · doi:10.1016/j.braindev.2004.09.008 · Cited by 62 · see citing works
JASPAC: Japan Spastic Paraplegia Research Consortium
Koh, K., Ishiura, H., Tsuji, S., et al. (2018) · Brain Sciences · doi:10.3390/brainsci8080153 · Cited by 50 · see citing works
Coll, M., Palau, N., Camps, C., Ruíz, M., Pàmpols, T., & Girós, M. (2005) · Clinical Genetics · doi:10.1111/j.1399-0004.2005.00423.x · Cited by 42 · see citing works
Determination of 30 X-linked adrenoleukodystrophy mutations, including 15 not previously described
Lachtermacher, M., Seu�nez, H. N., Moser, A. B., Moser, H. W., & Smith, K. D. (2000) · Human Mutation · doi:10.1002/(sici)1098-1004(200004)15:4 · Cited by 36 · see citing works
Clinical and Genetic Aspects in Twelve Korean Patients with Adrenomyeloneuropathy
Park, H. J., Shin, H. Y., Kang, H., Choi, B., Suh, B. C., Kim, H. J., Choi, Y., Lee, P. H., & Kim, S. M. (2014) · Yonsei Medical Journal · doi:10.3349/ymj.2014.55.3.676 · Cited by 20 · see citing works
Clinical characteristics of Taiwanese patients with Hereditary spastic paraplegia type 5
Chou, C., Soong, B., Lin, K., Tsai, Y., Jih, K., Liao, Y., & Lee, Y. (2020) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51019 · Cited by 19 · see citing works
Self-citationUnmasking adrenoleukodystrophy in a cohort of cerebellar ataxia
Chen, Y., Lee, Y., Tsai, Y., Guo, Y., Hsiao, C.-T., Tsai, P., Huang, J., Liao, Y., & Soong, B. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177296 · Cited by 18 · see citing works
Self-citationJiang, M., Cai, Y.-N., Liang, C., Peng, M.-Z., Sheng, H., Fan, L.-P., Lin, R., Jiang, H., Huang, Y., & Liu, L. (2015) · Metabolic Brain Disease · doi:10.1007/s11011-015-9717-6 · Cited by 17 · see citing works
Nerve conduction studies in healthy Chinese: correlation with age, sex, height and skin temperature.
Lin, K.-H., Chan, M. H., & Wu, Z. (1993) · PubMed · Cited by 14 · see citing works
Chen, Y.-J., Wang, M.-W., Dong, E.-L., Lin, X.-H., Wang, N., Zhang, Z.-Q., Lin, X., & Chen, W.-J. (2019) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2019.06.008 · Cited by 11 · see citing works
Self-citationTriantafyllou, P., Economou, M. P., Vlachaki, E., Aggelaki, M., Athanassiou‐Metaxa, M., Michelakaki, E., & Zafeiriou, D. (2014) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2014.01.027 · Cited by 9 · see citing works
Li, J., Wang, H., He, Z., Wang, X., Tang, J. P., & Huang, D. (2019) · BMC Neurology · doi:10.1186/s12883-019-1449-5 · Cited by 9 · see citing works
Role for peroxisome proliferator-activated receptor-gamma in Alzheimer's disease.
van Geel (2001) · Open Repository and Bibliography (University of Luxembourg) · doi:10.1002/1531-8249(20010201)49:2 · Cited by 7 · see citing works
Luo, W., Wei, Q., Dong, H., Yan, Y., Chen, M., & Li, H. (2019) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.1065 · Cited by 7 · see citing works
Hung, K., Wang, J.-S., Keng, W. T., Chen, H.-J., Liang, J., Ngu, L. H., & Lu, J. (2013) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2013.04.021 · Cited by 5 · see citing works
A Novel ABCD1 Gene Mutation in a Chinese-Taiwanese Patient with Adrenomyeloneuropathy
Liu, Y., Lin, K.-H., Soong, B.-W., Kwong-Kum, L., & Lin, K. (2007) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2006.12.009 · Cited by 3 · see citing works
Unmasking adrenoleukodystrophy in a cohort of cerebellar ataxia
Chen, Y. H., Lee, Y. C., Liao, Y., et al. (2017) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2017.08.854 · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Investigating KIF1A mutations in a Taiwanese cohort with hereditary spastic paraplegia
Hsu, S., Liao, Y., Lin, K., et al. (2022) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2022.09.001 · Cited by 5 · see citing works
Self-citationChang, M. C., & Yang, S. (2026) · Journal of International Medical Research · doi:10.1177/03000605261431607 · Cited by 1 · see citing works
“…ABCD1 mutations can produce a phenotype closely resembling HSP, suggesting an overlapping clinical spectrum between X-ALD and HSP. 3,8,14 Hsu et al. 14 further emphasized that ABCD1 mutations can underlie HSP-like presentations and recommended ABCD1 gene analysis in patients with clinically…”
InfluentialCarretero‐Vilarroig, L., Sivera, R., Baviera‐Muñoz, R., et al. (2026) · European Journal of Neurology · doi:10.1111/ene.70475
“In fact, it has explained a small proportion of patients in other HSP cohorts [26, 27].”
- Authors
- Hsu, S.-L., Chen, Y.-H., Chou, C.-T., Chou, Y.-T., Tsai, Y.-S., Hsiao, C.-T., Liao, Y.-C., & Lee, Y.-C.
- Affiliations
- National Yang Ming Chiao Tung University (TW)
- Taichung Veterans General Hospital (TW)
- Taipei Veterans General Hospital (TW)
- Corresponding author
- Liao, Yi-Chu
- Lee, Yi-Chung
- ORCID
- Venue
- Parkinsonism & Related Disorders
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 92
- Pages
- 7-12
- ISSN
- 1353-8020 (ISSN-L)
- OpenAlex
- W3205997769
- Semantic Scholar
- 674e9d1ad97e004e2c47b7efef2fdc4d8473b877
- Cited by
- 3
- References
- 30
- Citations by year
- 2026: 2 · 2022: 1
- FWCI
- 0.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Parkinsonism & Related Disorders (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- ABCD1 mutations, hereditary spastic paraplegia
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Adrenoleukodystrophy, Adult, DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Mutation, Phenotype, Taiwan, Cohort Studies, Spastic Paraplegia, Hereditary, Age of Onset, Asian People, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
