Leukoencephalopathy With Predominant Infratentorial Involvement Caused by a Novel ABCD1 Mutation: Does the Spinocerebellar Variant of Adrenoleukodystrophy Exist?

Neurologist. 2019 Nov;24(6):194-197. doi: 10.1097/NRL.0000000000000252.

Abstract

Introduction: X-linked adrenoleukodystrophy (X-ALD) encompasses several clinical and neuroimaging phenotypes, including cerebral X-ALD, the most common phenotype in children, and adrenomyeloneuropathy, the most common phenotype in adults. A spinocerebellar variant of X-ALD has been described in individuals from the Far East, but the criteria for its diagnosis are unclear.

Case report: A 35-year-old man from Albania was assessed because of a familial, slowly progressive spastic-ataxic gait associated with neurogenic bladder, sexual dysfunctions, and manic-like behavior. There was no definite clinical feature that suggested cerebellar involvement (eg, cerebellar limb ataxia, nystagmus, and dysarthria). A few months earlier, he had received a diagnosis of Addison disease. Brain magnetic resonance imaging showed a leukoencephalopathy with predominant cerebellum and brainstem involvement, and FDG-PET revealed marked cerebellar hypometabolism. The diagnosis of X-ALD was made because we found an increase of very long chain fatty acids, and a new ABCD1 mutation (c.1627C>T, p.Pro543Ser).

Conclusions: X-ALD should be included in the differential diagnosis of adult leukoencephalopathies with predominant involvement of infratentorial structures, that is, the cerebellum and brainstem. From a classification perspective, our patient (of white origin), like others (all of Asian origin), should be considered as suffering from a variant of adrenomyeloneuropathy rather than from spinocerebellar X-ALD. Actually, the term "spinocerebellar" or similar ones, such as "cerebello-brainstem dominant form," should be limited to those exceptional cases, in which both the clinical and neuroimaging findings point exclusively (or at least predominantly) to the involvement of infratentorial structures.

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1 / genetics*
  • Adrenoleukodystrophy / diagnosis*
  • Adrenoleukodystrophy / genetics*
  • Adrenoleukodystrophy / pathology
  • Adult
  • Brain Stem / pathology
  • Cerebellum / pathology*
  • Humans
  • Male
  • White Matter / pathology

Substances

  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1