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Initial frontal lobe involvement in adult cerebral X-linked adrenoleukodystrophy

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Abstract

Objective

Adult cerebral X-linked adrenoleukodystrophy (ACALD) with initial frontal lobe involvement is a rare genetic disease that is easily misdiagnosed and underdiagnosed. We sought to improve the early identification of such diseases.

Methods

We present three cases of adult X-linked adrenoleukodystrophy (ALD) with initial frontal lobe involvement and identify an additional 13 cases from the database. The clinical and imaging characteristics of the overall sixteen cases were analyzed.

Results

The average age of onset was 37 years, with 15 male and 1 female patient. A total of 12 patients (75%) developed a decline in cerebral executive and cognitive functions. Brain trauma is the possible trigger for the onset of ALD in five patients (31%). An elevated level of very-long-chain fatty acids (VLCFA) was observed in all 15 patients on whom a plasma VLCFA was performed.10 patients with gene tests showed different mutation sites in the ABCD1 gene. Brain MRI of six patients (46%) were characterized by frontal lobe “butterfly wings"-like lesions with peripheral rim enhancement. Four patients underwent brain biopsies (patients 1, 3, 15, and 13), and five patients (31%) were initially misdiagnosed (patients 1, 2, 3, 11, and 15). Nine of the patients with follow-up records experienced poor prognoses, and five of them, unfortunately, died (56%).

Conclusion

ACALD patients with anterior patterns tend to be misdiagnosed. The early clinical manifestation is a decline in cerebral executive and cognitive function. Brain trauma may be a trigger for this pattern. Brain MRI findings are characterized by frontal lobe “butterfly wing”-like lesions with peripheral rim enhancement. The determination of the VLCFA levels and the genetic detection of the causative mutations are required to confirm the diagnosis.

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All data processed in this paper are available, except some involved in patient privacy cannot be shared publicly.

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Acknowledgements

We thank the patients for their participation in this study.

Funding

The authors did not receive support from any organization for the submitted work.

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Author notes

  1. Wei Jiang and Wei Jin have contributed equally to this article.

Authors and Affiliations

  1. Department of Neurology, The First Medical Centre of Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China

    Wei Jiang, Dehui Huang & Lei Wu

  2. Department of Neurosurgery, The First Medical Centre of Chinese PLA General Hospital, Beijing, 100853, China

    Hulin Zhao

  3. Department of Pathology, The First Medical Centre of Chinese PLA General Hospital, Beijing, 100853, China

    Wei Jin

  4. Department of Neurology, The First Hospital, Changsha, 410005, Hunan, China

    Wei Jiang

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  1. Wei Jiang
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Correspondence to Dehui Huang or Lei Wu.

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This research was approved by the Ethics Committees of the First Medical Centre of Chinese PLA General Hospital in Beijing. Written informed consent was obtained from all patients.

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Jiang, W., Jin, W., Zhao, H. et al. Initial frontal lobe involvement in adult cerebral X-linked adrenoleukodystrophy. Acta Neurol Belg 123, 2259–2268 (2023). https://doi.org/10.1007/s13760-023-02295-x

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