Local Case – Man Diagnosed with MSA During Life But X-ALD Upon Brain Donation

This email may be of most interest if you are dealing with MSA that began younger than average with atypical symptoms.  Or if you are interested in what can be learned from post-mortem studies of brains of people diagnosed with MSA while alive.

This article in the journal Neuropathology was published yesterday.  I’m certain it is about a local support group member whose husband supposedly had MSA but, upon brain donation, it was identified that he had a very rare disorder called X-linked adrenoleukodystrophy (X-ALD).  This is the same disorder as the child in Lorenzo’s Oil had.   I believe this disease may be inherited but the donor had no living relatives to investigate.  Note that there is no treatment for adult-onset X-ALD.

The donor had neurological symptoms for over 30 years, and died last year at the age of 69.  The last several years of his life, he was diagnosed with MSA because of cerebellar ataxia, gait problems, speech problems, and autonomic dysfunction.  “A diagnosis of X-ALD was never entertained during his life. He had long disease duration (35 years) and lacked characteristic MRI findings of X-ALD (and of MSA).”

There are only 33 other cases of cerebello-brainstem dominant X-ALD reported worldwide.  Most of the other cases had a family history of X-ALD or Addison’s Disease, adrenal insufficiency or T2-weighted hyperintensities in certain brain areas on MRI.  Our local support group member’s husband had none of these characteristics.  In his case, the “T2 signal abnormalities were interpreted as being due to microvascular pathology common in aging.”  Note that most of the other cases are from Japan and South Korea.

Despite the rarity of X-ALD, the researchers argue that X-ALD should be considered as a differential diagnosis in MSA, especially in younger patients with atypical symptoms.  This sounds like a red herring to me, but I’m anxious to ask some neurologists about this idea.

The Discussion section of the article is interesting in that it reviews details and comparisons of the 34 confirmed X-ALD cases.  I think this is enough for most of you but if you want more, check out the full article.  I’ve also copied the abstract below.



Neuropathology. 2015 Jul 31.Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review.

Ogaki K, Koga S, Aoki N, Lin W, Suzuki K, Ross OA, Dickson DW.

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 34 years. 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 69 years 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.

© 2015 Japanese Society of Neuropathology.

PMID:  26227820