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Addictive substances may induce a rapid neurological deterioration in fragile X-associated tremor ataxia syndrome: A report of two cases.

ABSTRACT: A debilitating late-onset disorder of the premutation in the FMR1 gene is the neurodegenerative disorder fragile X-associated tremor ataxia syndrome (FXTAS). We report two patients with FXTAS who have a history of substance abuse (opiates, alcohol, and cocaine) which may have exacerbated their rapid neurological deterioration with FXTAS. There has been no case report regarding the role of substance abuse in onset, progression, and severity of FXTAS symptoms. However, research has shown that substance abuse can have a negative impact on several neurodegenerative diseases, and we propose that in these cases, substance abuse contributed to a faster progression of FXTAS as well as exacerbated white matter disease.

SUBMITTER: Muzar Z

PROVIDER: S-EPMC4298646 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Addictive substances may induce a rapid neurological deterioration in fragile X-associated tremor ataxia syndrome: A report of two cases.

Muzar Zukhrofi Z Adams Patrick E PE Schneider Andrea A Hagerman Randi J RJ Lozano Reymundo R

Intractable & rare diseases research 20141101 4

A debilitating late-onset disorder of the premutation in the FMR1 gene is the neurodegenerative disorder fragile X-associated tremor ataxia syndrome (FXTAS). We report two patients with FXTAS who have a history of substance abuse (opiates, alcohol, and cocaine) which may have exacerbated their rapid neurological deterioration with FXTAS. There has been no case report regarding the role of substance abuse in onset, progression, and severity of FXTAS symptoms. However, research has shown that subs ...[more]

PMID: 25606366

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Project description:Since its discovery in 2001, our understanding of fragile X-associated tremor/ataxia syndrome (FXTAS) has undergone a remarkable transformation. Initially characterized rather narrowly as an adult-onset movement disorder, the definition of FXTAS is broadening; moreover, the disorder is now recognized as only one facet of a much broader clinical pleiotropy among children and adults who carry premutation alleles of the FMR1 gene. Furthermore, the intranuclear inclusions of FXTAS, once thought to be a CNS-specific marker of the disorder, are now known to be widely distributed in multiple non-CNS tissues; this observation fundamentally changes our concept of the disease, and may provide the basis for understanding the diverse medical problems associated with the premutation. Recent work on the pathogenic mechanisms underlying FXTAS indicates that the origins of the late-onset neurodegenerative disorder actually lie in early development, raising the likelihood that all forms of clinical involvement among premutation carriers have a common underlying mechanistic basis. There has also been great progress in our understanding of the triggering event(s) in FXTAS pathogenesis, which is now thought to involve sequestration of one or more nuclear proteins involved with microRNA biogenesis. Moreover, there is mounting evidence that mitochondrial dysregulation contributes to the decreased cell function and loss of viability, evident in mice even during the neonatal period. Taken together, these recent findings offer hope for early interventions for FXTAS, well before the onset of overt disease, and for the treatment of other forms of clinical involvement among premutation carriers.

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