Ann Clin Neurophysiol.  2021 Apr;23(1):61-64. 10.14253/acn.2021.23.1.61.

Adrenomyeloneuropathy with cerebral involvement due to a novel frameshift variant in ABCD1 gene

• Kim HW
• Kim H
• Jeong D
• Chung K
• Lee EJ
• Lim YM
• Kim KK

• KMID: 2515610
• DOI: http://doi.org/10.14253/acn.2021.23.1.61

Abstract

Adrenoleukodystrophy (ALD) is the most common peroxisomal disorder caused by mutations in the gene, ABCD1, causing abnormal accumulation of very-long-chain fatty acids in the nervous system and adrenal glands. There are various clinical manifestations of ALD. Here we report a 47-year-old male with adrenomyeloneuropathy with cerebral involvement who exhibited progressive gait disturbance and cognitive impairment. A novel frameshift variant (c.95del [p.Val32Alafs*36]) in exon 1 of ABCD1 was identified. This report provides additional information regarding the various clinical characteristics of ALD.

Keyword

Adrenoleukodystrophy; Phenotype

Figure

• 

  Fig. 1. Pedigree of the patient. The arrow indicates the proband.

• 

  Fig. 2. Brain magnetic resonance imaging of the patient. Axial fluid-attenuated inversion recovery images showing increased signal intensities in the bilateral corticospinal tract (A), the splenium of the corpus callosum and the bilateral occipital subcortex (B), and the bilateral frontoparietal subcortex (C).

• 

  Fig. 3. Sanger sequencing chromatogram of the patient. Sequencing analysis revealed a deletion in exon 1 of ABCD1 (arrow, c.95del), which is a frameshift variant that causes premature termination of translation (p.Val32Alafs*36).

Reference

1. Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R, Moser H, et al. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature. 1993; 361:726–730.

2. Boehm CD, Cutting GR, Lachtermacher MB, Moser HW, Chong SS. Accurate DNA-based diagnostic and carrier testing for X-linked adrenoleukodystrophy. Mol Genet Metab. 1999; 66:128–136.

3. Pavlakis SG. New insights into adrenoleukodystrophy. Eur J Paediatr Neurol. 2017; 21:597.

4. Kemp S, Huffnagel IC, Linthorst GE, Wanders RJ, Engelen M. Adrenoleukodystrophy-neuroendocrine pathogenesis and redefinition of natural history. Nat Rev Endocrinol. 2016; 12:606–615.

5. Berger J, Forss-Petter S, Eichler FS. Pathophysiology of X-linked adrenoleukodystrophy. Biochimie. 2014; 98:135–142.

6. Park HJ, Shin HY, Kang HC, Choi BO, Suh BC, Kim HJ, et al. Clinical and genetic aspects in twelve Korean patients with adrenomyeloneuropathy. Yonsei Med J. 2014; 55:676–682.

7. Vanderver A. Genetic leukoencephalopathies in adults. Continuum (Minneap Minn). 2016; 22:916–942.

8. Köhler W, Curiel J, Vanderver A. Adulthood leukodystrophies. Nat Rev Neurol. 2018; 14:94–105.

9. Eichler F, Duncan C, Musolino PL, Orchard PJ, De Oliveira S, Thrasher AJ, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med. 2017; 377:1630–1638.

10. Gong Y, Mu D, Prabhakar S, Moser A, Musolino P, Ren J, et al. Adenoassociated virus serotype 9-mediated gene therapy for x-linked adrenoleukodystrophy. Mol Ther. 2015; 23:824–834.