SpringerLink
Log in

Typical and atypical phenotype and neuroimaging of X-linked adrenoleukodystrophy in a Chinese cohort

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Objective

The objective of this study is to describe the typical and atypical clinical and neuroimaging features of ALD in Chinese patients, which will help early diagnosis and intervention to improve prognosis of ALD.

Methods

Forty-one patients in the Leukoencephalopathy Clinic of Neurology Department, Peking Union Medical College Hospital were enrolled. Detailed clinical manifestations and MRI features were analyzed. The relationship between phenotype and genotype as well as biochemical analysis was observed.

Results

The patients were classified according to phenotype and onset age, including 14 childhood cerebral ALD (CCALD), 8 adolescent cerebral ALD (adoCALD), 3 adult cerebral ALD (ACALD), 14 adrenomyeloneuropathy (AMN), and 2 ALD in women. AMN was the main presentation in adults. Visual impairment was usual onset symptom in CCALD and cognitive decline and psychiatric symptoms were found in adoCALD and ACALD. Typical MRI feature of CALD was symmetrical peri-ventricular “butterfly wings” like lesions in frontal and/or occipital lobe with peripheral DWI hyperintensities and Gd enhancement. Corpus callosum and internal capsule were always involved. Unilateral lesions were also possible. Cerebral AMN presented with centrum semiovale diffuse involvement. Spinocerebellar variant was a special subtype of AMN with obvious cerebellar and brainstem lesions. No relationships between phenotype and genotype as well as biochemical VLCFAs analysis were found.

Conclusions

We emphasize that corpus callosum and internal capsule are always involved in ALD. A unilateral lesion is also possible. Neuroimaging of cerebral AMN is different from typical CALD with more centrum semiovale involvement. We support spinocerebellar variant was a rare subtype of AMN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kemp S, Berger J, Aubourg P (2012) X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta 1822:1465–1474. https://doi.org/10.1016/j.bbadis.2012.03.012

    Article  CAS  PubMed  Google Scholar 

  2. Engelen M, Kemp S, Poll-The BT (2014) X-linked adrenoleukodystrophy: pathogenesis and treatment. Curr Neurol Neurosci Rep 14:486. https://doi.org/10.1007/s11910-014-0486-0

    Article  CAS  PubMed  Google Scholar 

  3. Engelen M, Kemp S, de Visser M et al (2012) X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis 7:51. https://doi.org/10.1186/1750-1172-7-51

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kemp S, Wanders R (2010) Biochemical aspects of X-linked adrenoleukodystrophy. Brain Pathol 20:831–837. https://doi.org/10.1111/j.1750-3639.2010.00391.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Eichler F, Duncan C, Musolino PL et al (2017) Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med 377:1630–1638. https://doi.org/10.1056/NEJMoa1700554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jia MR, Wu WZ, Li CM et al (2019) Clinical characteristics and phenotype distribution in 10 Chinese patients with X-linked adrenoleukodystrophy. Exp Ther Med 18:1945–1952. https://doi.org/10.3892/etm.2019.7804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Eng L, Regelmann MO (2019) Early onset primary adrenal insufficiency in males with adrenoleukodystrophy: case series and literature review. J Pediatr 211:211–214. https://doi.org/10.1016/j.jpeds.2019.04.021

    Article  PubMed  Google Scholar 

  8. Tran C, Patel J, Stacy H et al (2017) Long-term outcome of patients with X-linked adrenoleukodystrophy: a retrospective cohort study. Eur J Paediatr Neurol 21:600–609. https://doi.org/10.1016/j.ejpn.2017.02.006

    Article  PubMed  Google Scholar 

  9. Ferrer I, Aubourg P, Pujol A (2010) General aspects and neuropathology of X-linked adrenoleukodystrophy. Brain Pathol 20:817–830. https://doi.org/10.1111/j.1750-3639.2010.00390.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Liberato AP, Mallack EJ, Aziz-Bose R et al (2019) MRI brain lesions in asymptomatic boys with X-linked adrenoleukodystrophy. Neurology 92:e1698–e1708. https://doi.org/10.1212/WNL.0000000000007294

    Article  PubMed  PubMed Central  Google Scholar 

  11. Engelen M, Barbier M, Dijkstra IM et al (2014) X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. Brain 137:693–706. https://doi.org/10.1093/brain/awt361

    Article  PubMed  Google Scholar 

  12. Lin JE, Armour EA, Heshmati A et al (2019) Pearls & Oy-sters: adolescent-onset adrenomyeloneuropathy and arrested cerebral adrenoleukodystrophy. Neurology 93:81–84. https://doi.org/10.1212/WNL.0000000000007755

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chen YJ, Wang MW, Dong EL et al (2019) Chinese patients with adrenoleukodystrophy and Zellweger spectrum disorder presenting with hereditary spastic paraplegia. Parkinsonism Relat Disord 65:256–260. https://doi.org/10.1016/j.parkreldis.2019.06.008

    Article  PubMed  Google Scholar 

  14. Luo WJ, Wei Q, Dong HL, Yan YT, Chen MJ, Li HF (2020) Spastic paraplegia as the predominant phenotype in a cohort of Chinese patients with adrenoleukodystrophy. Mol Genet Genomic Med 8:e1065. https://doi.org/10.1002/mgg3.1065

    Article  PubMed  Google Scholar 

  15. Azar C, Shor N, Nadjar Y (2020) Adrenomyeloneuropathy masquerading as chronic myelitis. JAMA Neurol 77:522–523. https://doi.org/10.1001/jamaneurol.2020.0019

    Article  PubMed  Google Scholar 

  16. Huffnagel IC, Dijkgraaf M, Janssens GE et al (2019) Disease progression in women with X-linked adrenoleukodystrophy is slow. Orphanet J Rare Dis 14:30. https://doi.org/10.1186/s13023-019-1008-6

    Article  PubMed  PubMed Central  Google Scholar 

  17. Dubey P, Fatemi A, Huang H et al (2005) Diffusion tensor based imaging reveals occult abnormalities in adrenomyeloneuropathy. Ann Neurol 58:758–766. https://doi.org/10.1002/ana.20643

    Article  PubMed  Google Scholar 

  18. Qiu Y, **n L, Wang Y et al (2018) Novel ABCD 1 gene mutaion in adrenomyeloneuropathy with hypoplasia and agenesis of the corpus callosum. Neurodegener Dis 18:156–164. https://doi.org/10.1159/000490248

    Article  CAS  PubMed  Google Scholar 

  19. van Geel BM, Bezman L, Loes DJ, Moser HW, Raymond GV (2001) Evolution of phenotypes in adult male patients with X-linked adrenoleukodystrophy. Ann Neurol 49:186–194. https://doi.org/10.1002/1531-8249(20010201)49:2%3c186::aid-ana38%3e3.0.co;2-r

    Article  PubMed  Google Scholar 

  20. Au L, Chan A, Mok V (2019) Teaching neuroimages: X-linked adrenoleukodystrophy: spinocerebellar variant. Neurology 93:e731–e732. https://doi.org/10.1212/WNL.0000000000007958

    Article  PubMed  Google Scholar 

  21. Ogaki K, Koga S, Aoki N et al (2016) Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review. Neuropathology 36:64–76. https://doi.org/10.1111/neup.12230

    Article  PubMed  Google Scholar 

  22. Benzoni C, Farina L, Pensato V et al (2019) Leukoencephalopathy with predominant infratentorial involvement caused by a novel ABCD1 mutation: does the spinocerebellar variant of adrenoleukodystrophy exist. Neurologist 24:194–197. https://doi.org/10.1097/NRL.0000000000000252

    Article  PubMed  Google Scholar 

  23. Kemp S, Pujol A, Waterham HR et al (2001) ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Hum Mutat 18:499–515. https://doi.org/10.1002/humu.1227

    Article  CAS  PubMed  Google Scholar 

  24. Herman M, Jura M, Krakowska K, Barg E (2019) X-linked adrenoleukodystrophy diagnosed in three brothers. Pediatr Endocrinol Diabetes Metab 25:95–98. https://doi.org/10.5114/pedm.2019.85821

    Article  PubMed  Google Scholar 

  25. Mehrpour M, Gohari F, Dizaji MZ, Ahani A, Malicdan MC, Behnam B (2016) An ABCD1 mutation (c.253dupC) caused diverse phenotypes of adrenoleukodystrophy in an Iranian consanguineous pedigree. J Mol Genet Med 10:222. https://doi.org/10.4172/1747-0862.1000222

    Article  CAS  PubMed  Google Scholar 

  26. Chu SS, Ye J, Zhang HW et al (2015) Eight novel mutations in the ABCD1 gene and clinical characteristics of 25 Chinese patients with X-linked adrenoleukodystrophy. World J Pediatr 11:366–373. https://doi.org/10.1007/s12519-015-0044-0

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the patients for participating in this study.

Funding

This work was supported by National Key Research and Development Program of China (2020YFA0804500); CAMS Innovation Fund for Medical Sciences (CIFMS) (Nos. 2020-I2M-C&T-B-010, 2016-I2M-1–004); and National Natural Science Foundation of China (81550021, 30470618).

Author information

Authors and Affiliations

  1. Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Bei**g, 100730, China

    Chenhui Mao, Jie Li, **nying Huang, Jie Wang, Shanshan Chu, Yao Zhang, Liling Dong, Caiyan Liu, Bin Peng, Liying Cui & **g Gao

  2. Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Bei**g, 100730, China

    Lin Lu

  3. Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Bei**g, 100730, China

    Ling Qiu

  4. Department of Clinical Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Bei**g, 100730, China

    Wei Chen

Authors
  1. Chenhui Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. **nying Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shanshan Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liling Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Caiyan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ling Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Wei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Bin Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Liying Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. **g Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: [Chenhui Mao], [**g Gao]; methodology: [Chenhui Mao]; formal analysis and investigation: [Jie Li], [**nying Huang], [Jie Wang], [Shanshan Chu], [Yao Zhang], [Liling Dong], [Caiyan Liu]; writing—original draft preparation: [Chenhui Mao]; writing—review and editing: [Chenhui Mao],[Lin Lu], [Ling Qiu], [Wei Chen]; funding acquisition: [**g Gao], [Chenhui Mao]; resources: [**g Gao]; supervision: [**g Gao, Bin Peng, Liying Cui].

Corresponding author

Correspondence to **g Gao.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical standards

Written informed consent was obtained from the individuals and/or their parents for the publication of any potentially identifiable images or data included in this article. The ethics committee of Peking Union Medical College Hospital had approved the study (No. JS1836) and it had therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Chenhui Mao, Lin Lu, Ling Qiu, Wei Chen, and **g Gao are members of the Peking Union Medical College Hospital ALD Multi-disciplinary cooperating group.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mao, C., Li, J., Huang, X. et al. Typical and atypical phenotype and neuroimaging of X-linked adrenoleukodystrophy in a Chinese cohort. Neurol Sci 43, 3255–3263 (2022). https://doi.org/10.1007/s10072-021-05859-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-021-05859-y

Keywords

Search

Navigation