Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: Case report and literature review

Kotaro Ogaki, Shunsuke Koga, Naoya Aoki, Wenlang Lin, Kinuko Suzuki, Owen A Ross, Dennis W Dickson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy-confirmed cases exceedingly rare. We report a 69-year-old White man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison's disease. His initial symptom was temporary loss of eyesight at age 34years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69years with a diagnosis of MSA. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting the optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be considered in the differential diagnosis of MSA.

Original languageEnglish (US)
Pages (from-to)64-76
Number of pages13
JournalNeuropathology
Volume36
Issue number1
DOIs
StatePublished - Feb 1 2016

Fingerprint

Adrenoleukodystrophy
Multiple System Atrophy
Brain Stem
Cerebellum
Peroxisomal Disorders
Macrophages
Pathology
Internal Capsule
Addison Disease
Occipital Lobe
Adrenal Insufficiency
Cerebellar Ataxia
Mutation
Inclusion Bodies
Cerebrum
Myelin Sheath
Gait
Hearing Loss
Atrophy
Lower Extremity

Keywords

  • ABCD1
  • Adrenoleukodystrophy
  • Cerebello-brainstem dominant formmultiple system atrophy
  • Olivopontocerebellar atrophy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy : Case report and literature review. / Ogaki, Kotaro; Koga, Shunsuke; Aoki, Naoya; Lin, Wenlang; Suzuki, Kinuko; Ross, Owen A; Dickson, Dennis W.

In: Neuropathology, Vol. 36, No. 1, 01.02.2016, p. 64-76.

Research output: Contribution to journalArticle

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