Yonsei Med J.  2014 Jul;55(4):1157-1160. 10.3349/ymj.2014.55.4.1157.

Isolated Cerebellar Variant of Adrenoleukodystrophy with a de novo Adenosine Triphosphate-Binding Cassette D1 (ABCD1) Gene Mutation

• Kang JW
• Lee SM
• Koo KY
• Lee YM
• Nam HS
• Quan Z
• Kang HC

• KMID: 2130847
• DOI: http://doi.org/10.3349/ymj.2014.55.4.1157

Abstract

X-linked adrenoleukodystrophy (X-ALD) shows a wide range of phenotypic expression, but clinical presentation as an isolated lesion of the cerebellar white matter and dentate nuclei has not been reported. We report an unusual presentation of X-ALD only with an isolated lesion of the cerebellar white matter and dentate nuclei. The proband, a 37-year-old man presented with bladder incontinence, slurred speech, dysmetria in all limbs, difficulties in balancing, and gait ataxia. Brain magnetic resonance imaging showed an isolated signal change of white matter around the dentate nucleus in cerebellum. With high level of very long chain fatty acid, gene study showed a de novo mutation in exon 1 at nucleotide position c.277_296dup20 (p.Ala100Cysfs*10) of the adenosine triphosphate-binding cassette D1 gene. It is advised to consider X-ALD as a differential diagnosis in patients with isolated cerebellar degeneration symptoms.

Keyword

X-linked adrenoleukodystrophy; cerebellar; ABCD1; very long chain fatty acid

MeSH Terms

ATP-Binding Cassette Transporters/*genetics
Adrenoleukodystrophy/blood/*genetics
Adult
Cerebellar Diseases/blood/*genetics
Fatty Acids/blood
Humans
Male
Mutation
Fatty Acids

Figure

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  Fig. 1 Pedigree of the present family. The proband is indicated by an arrow. Affected males are designated by solid symbols and carrier females by circle with dot. Squares, male; circles, females.

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  Fig. 2 (A) T2 magnetic resonance imaging (MRI) of the brain showed hypointense lesions in the dentate nuclei on axial planes. (B) T2-fluid-attenuated inversion recovery MRI of the brain showed hyperintense lesions in the dentate nuclei on sagittal planes. (C) No contrast enhancement was seen in T1-gadolium enhancement MRI of the spinal cord on sagittal plane.

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  Fig. 3 Direct sequencing analysis of the proband with X-linked adrenoleukodystrophy demonstrated a novel duplication in exon 1 of adenosine triphosphate-binding cassette D1 gene, c.277_296dup20 (p.Ala100Cysfs*10). Box indicates position of the novel mutation.

Reference

1. Kemp S, Berger J, Aubourg P. X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta. 2012; 1822:1465–1474.

2. Moser HW, Moser AB, Smith KD, Bergin A, Borel J, Shankroff J, et al. Adrenoleukodystrophy: phenotypic variability and implications for therapy. J Inherit Metab Dis. 1992; 15:645–664.

3. Kusaka H, Imai T. Ataxic variant of adrenoleukodystrophy: MRI and CT findings. J Neurol. 1992; 239:307–310.

4. Dunne E, Hyman NM, Huson SM, Németh AH. A novel point mutation in X-linked adrenoleukodystrophy presenting as a spinocerebellar degeneration. Ann Neurol. 1999; 45:652–655.

5. Li JY, Hsu CC, Tsai CR. Spinocerebellar variant of adrenoleukodystrophy with a novel ABCD1 gene mutation. J Neurol Sci. 2010; 290:163–165.

6. Nakazato T, Sato T, Nakamura T, Tsuji S, Narabayashi H. Adrenoleukodystrophy presenting as spinocerebellar degeneration. Eur Neurol. 1989; 29:229–234.

7. Takada K, Onoda K, Takahashi K, Nakamura H, Taketomi T. An adult case of adrenoleukodystrophy with features of olivo-ponto-cerebellar atrophy: I. Clinical and pathological studies. Jpn J Exp Med. 1987; 57:53–58.

8. Tan EK, Lim SH, Chan LL, Wong MC, Tan KP. X-linked adrenoleukodystrophy: spinocerebellar variant. Clin Neurol Neurosurg. 1999; 101:137–140.

9. Vianello M, Manara R, Betterle C, Tavolato B, Mariniello B, Giometto B. X-linked adrenoleukodystrophy with olivopontocerebellar atrophy. Eur J Neurol. 2005; 12:912–914.

10. Suzuki Y, Takemoto Y, Shimozawa N, Imanaka T, Kato S, Furuya H, et al. Natural history of X-linked adrenoleukodystrophy in Japan. Brain Dev. 2005; 27:353–357.

11. Kurihara K, Kim H, Tamura N, Iwasaki S, Hamaguchi K. [A case of adrenoleukodystrophy presenting large lesion of the cerebellar white matter and dentate nuclei on brain CT and MRI]. Rinsho Shinkeigaku. 1991; 31:72–78.

12. Miyai I, Fujimura H, Umekage T, Watase K, Ueno S, Yorifuji S, et al. Magnetic resonance imaging in adrenoleukodystrophy presenting as spinocerebellar degeneration. J Neurol Neurosurg Psychiatry. 1990; 53:623–624.

13. Waragai M, Takaya Y, Hayashi M, Shibata N, Kobayashi M. MRI of adrenoleukodystrophy involving predominantly the cerebellum and brain stem. Neuroradiology. 1996; 38:788–791.

14. Mishra S, Modi M, Das CP, Prabhakar S. Adrenoleukodystrophy manifesting as spinocerebellar degeneration. Neurol India. 2006; 54:195–196.

15. Loes DJ, Fatemi A, Melhem ER, Gupte N, Bezman L, Moser HW, et al. Analysis of MRI patterns aids prediction of progression in X-linked adrenoleukodystrophy. Neurology. 2003; 61:369–374.

16. Elenein RA, Naik S, Kim S, Punia V, Jin K. Teaching neuroimages: cerebral adrenoleukodystrophy: a rare adult form. Neurology. 2013; 80:e69–e70.

17. Poll-The BT, Engelen M. Peroxisomal leukoencephalopathy. Semin Neurol. 2012; 32:42–50.