Journal of Shanghai Jiao Tong University (Medical Science) >

2023 , Vol. 43 >Issue 5: 592 - 599

DOI: https://doi.org/10.3969/j.issn.1674-8115.2023.05.009

Clinical research

Clinical and genetic characteristics of adult cerebral adrenoleukodystrophy

  • Taotao LIU ,
  • Xiaoli LIU ,
  • Jingying WU ,
  • Ruilong NI ,
  • Mengyuan ZHANG ,
  • Duxin JI ,
  • Mei ZHANG ,
  • Li CAO
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  • 1.Department of Neurology, Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
    2.Department of Neurology, The First Affiliated Hospital of Anhui University of Science and Technology, Huainan 232001, China
    3.Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai 201400, China
CAO Li, E-mail: caoli2000@yeah.net.

Received date: 2023-02-03

  Accepted date: 2023-05-06

  Online published: 2023-07-11

Supported by

National Natural Science Foundation of China(81870889)

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Abstract

Objective ·To summarize and analyze the clinical and genetic characteristics of adult cerebral adrenoleukodystrophy(ACALD ). Methods ·The data of eight patients with ACALD who attended the Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2018 to September 2022 were collected and comprehensively analyzed. Clinical data included age at onset, duration of disease, family history, present history and physical examination. Imaging examinations included magnetic resonance imaging (MRI) of the cranial, cervical spine and thoracic spine. Laboratory tests included serum very-long-chain fatty acids (VLCFA), adrenal cortical function and genetic test. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (Moca) were used to assess patients′ cognitive function. Results ·A total of 8 male patients with ACALD were included in this study. Ageat onset ranged from 23 to 40 years old with an average age of (32.75±5.80) years, and the disease duration ranged from 4 to 59 months. Patients′ first symptoms were highly variable. Three patients showed memory loss and cognitive dysfunction, two showed irritability and personality change, one showed mental and behavioral abnormalities, one showed dysarthria and ataxia, and one showed persistent dizziness, occipital numbness and insomnia. All the patients had multiple white matter demyelination lesions, and white matter demyelination in parietal occipital lobe and posterior corpus callosum was the most common. Enhancement MRI showed patchy Gd-enhancement of partial lesions in three cases. In two patients, magnetic resonance spectroscopy showed that choline (Cho) peak increased and N-acetyl-aspartate (NAA) peak decreased. Serum VLCFA levels of C26, C24/C22 and C26/C22 were elevated in six patients who underwent serum VLCFA examination. Seven patients underwent adrenal cortical function testing, of which six experienced adrenal cortical dysfunction. Six patients were cognitively impaired, four of whom had decreased MMSE and MoCA scores, and two of whom were unable to cooperate with the assessment due to severe cognitive impairment. Eight different ABCD1 gene mutations were identified, among which c.1750delC (p.H584Tfs*52) and c.160_170delACGCAGGAGGC (p.T54Lfs*137) were novel mutations. Conclusion ·The initial symptoms of ACALD vary, among which memory loss and cognitive dysfunction are the most common. White matter demyelination lesions in the parietal and corpus callosum pressure are the most common, and imaging abnormalities precede neurological symptoms. The clinical features of the disease are hair thinning and skin pigmentation, and the biochemical features are elevated serum VLCFA and adrenal insufficiency. Missense mutations are more common in the ABCD1 gene, and exons 1 and 6 are the hot mutant exons in Chinese.

Key words： adrenoleukodystrophy(ACALD); genetic diseases; X-linked; cognition disorders; demyelinating diseases; adrenal insufficiency

Cite this article

Taotao LIU , Xiaoli LIU , Jingying WU , Ruilong NI , Mengyuan ZHANG , Duxin JI , Mei ZHANG , Li CAO . Clinical and genetic characteristics of adult cerebral adrenoleukodystrophy[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023 , 43(5) : 592 -599 . DOI: 10.3969/j.issn.1674-8115.2023.05.009

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