scholarly journals Fragile-X-Associated Tremor/Ataxia Syndrome or Alcohol-Induced Cerebellar Degeneration? A Case Report

2020 ◽  
Vol 12 (3) ◽  
pp. 466-471
Author(s):  
Giulia Grigioni ◽  
Christian Saleh ◽  
Phillip Jaszczuk ◽  
Dorothea Wand ◽  
Stefanie Wilmes ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Case Report ◽  
Neurodegenerative Disorder ◽  
Fragile X ◽  
Disease Diagnosis ◽  
Cerebellar Degeneration ◽  
Gait Ataxia ◽  
Intention Tremor ◽  
Triplet Expansion ◽  
Ataxia Syndrome

Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that manifests with intention tremor, progressive gait ataxia, and cognitive impairment. The disease is genetically characterized by a premutation of the <i>FMR1</i>gene on the X-chromosome manifesting with a CGG triplet expansion between 55 and 200. Given the phenotypical variety of this disease, diagnosis is frequently delayed. We present and discuss a male patient whose diagnosis of FXTAS was delayed due to his concomitant alcohol abuse.

scholarly journals The fragile x-associated tremor and ataxia syndrome (FXTAS)

2010 ◽  
Vol 68 (5) ◽  
pp. 791-798 ◽  
Author(s):  
Leonardo Pires Capelli ◽  
Márcia Rúbia Rodrigues Gonçalves ◽  
Claudia C Leite ◽  
Egberto R Barbosa ◽  
Ricardo Nitrini ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Current Knowledge ◽  
Fragile X ◽  
Gait Ataxia ◽  
Intention Tremor ◽  
Full Mutation ◽  
Clinical Genetic ◽  
Diagnostic Aspects ◽  
Ataxia Syndrome

FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.

scholarly journals Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes

2021 ◽  
Vol 22 (16) ◽  
pp. 8368
Author(s):  
Luis M. Valor ◽  
Jorge C. Morales ◽  
Irati Hervás-Corpión ◽  
Rosario Marín
Keyword(s):  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Fragile X ◽  
Endocrine System ◽  
Molecular Pathogenesis ◽  
Adult Women ◽  
Adult Men ◽  
Cgg Repeats ◽  
Reproductive Impairment ◽  
Ataxia Syndrome

Abnormal trinucleotide expansions cause rare disorders that compromise quality of life and, in some cases, lifespan. In particular, the expansions of the CGG-repeats stretch at the 5’-UTR of the Fragile X Mental Retardation 1 (FMR1) gene have pleiotropic effects that lead to a variety of Fragile X-associated syndromes: the neurodevelopmental Fragile X syndrome (FXS) in children, the late-onset neurodegenerative disorder Fragile X-associated tremor-ataxia syndrome (FXTAS) that mainly affects adult men, the Fragile X-associated primary ovarian insufficiency (FXPOI) in adult women, and a variety of psychiatric and affective disorders that are under the term of Fragile X-associated neuropsychiatric disorders (FXAND). In this review, we will describe the pathological mechanisms of the adult “gain-of-function” syndromes that are mainly caused by the toxic actions of CGG RNA and FMRpolyG peptide. There have been intensive attempts to identify reliable peripheral biomarkers to assess disease progression and onset of specific pathological traits. Mitochondrial dysfunction, altered miRNA expression, endocrine system failure, and impairment of the GABAergic transmission are some of the affectations that are susceptible to be tracked using peripheral blood for monitoring of the motor, cognitive, psychiatric and reproductive impairment of the CGG-expansion carriers. We provided some illustrative examples from our own cohort. Understanding the association between molecular pathogenesis and biomarkers dynamics will improve effective prognosis and clinical management of CGG-expansion carriers.

scholarly journals Altered Redox Mitochondrial Biology in the Neurodegenerative Disorder Fragile X-Tremor/Ataxia Syndrome: Use of Antioxidants in Precision Medicine

2016 ◽  
Vol 22 (1) ◽  
pp. 548-559 ◽  
Author(s):  
Gyu Song ◽  
Eleonora Napoli ◽  
Sarah Wong ◽  
Randi Hagerman ◽  
Siming Liu ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Neurodegenerative Disorder ◽  
Fragile X ◽  
Ataxia Syndrome

Cognitive Impairment in a 65-year-old Male With the Fragile X-associated Tremor-Ataxia Syndrome (FXTAS)

2006 ◽  
Vol 19 (3) ◽  
pp. 165-171 ◽  
Author(s):  
Jim Grigsby ◽  
Maureen A. Leehey ◽  
S??bastien Jacquemont ◽  
James A. Brunberg ◽  
Randi J. Hagerman ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Fragile X ◽  
Ataxia Syndrome

scholarly journals Deep brain stimulation or thalamotomy in fragile X-associated tremor/ataxia syndrome? Case report

2016 ◽  
Vol 50 (4) ◽  
pp. 303-308 ◽  
Author(s):  
Gertrúd Tamás ◽  
Norbert Kovács ◽  
Noémi Ágnes Varga ◽  
Péter Barsi ◽  
Loránd Erőss ◽  
...  
Keyword(s):  
Case Report ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Fragile X ◽  
Ataxia Syndrome ◽  
Deep Brain

scholarly journals Risk Factors for Cognitive Impairment in Fragile X-Associated Tremor/Ataxia Syndrome

2016 ◽  
Vol 29 (6) ◽  
pp. 328-337 ◽  
Author(s):  
Andreea L. Seritan ◽  
Kyoungmi Kim ◽  
Ian Benjamin ◽  
Ioana Seritan ◽  
Randi J. Hagerman
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Fragile X ◽  
Ataxia Syndrome

scholarly journals Human Cerebral Cortex Proteome of Fragile X-Associated Tremor/Ataxia Syndrome

2021 ◽  
Vol 7 ◽  
Author(s):  
Katharine Nichole Holm ◽  
Anthony W. Herren ◽  
Sandra L. Taylor ◽  
Jamie L. Randol ◽  
Kyoungmi Kim ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Structural Integrity ◽  
Rna Binding ◽  
Neurodegenerative Disorder ◽  
Fragile X ◽  
Protein Abundance ◽  
Cgg Repeat ◽  
Phosphoserine Aminotransferase ◽  
Brain Volume Loss ◽  
Ataxia Syndrome

Background: Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder associated with premutation CGG-repeat expansions (55–200 repeats) in the 5′ non-coding portion of the fragile X mental retardation 1 (FMR1) gene. Core features of FXTAS include progressive tremor/ataxia, cognitive decline, variable brain volume loss, and white matter disease. The principal histopathological feature of FXTAS is the presence of central nervous system (CNS) and non-CNS intranuclear inclusions.Objective: To further elucidate the molecular underpinnings of FXTAS through the proteomic characterization of human FXTAS cortexes.Results: Proteomic analysis of FXTAS brain cortical tissue (n = 8) identified minor differences in protein abundance compared to control brains (n = 6). Significant differences in FXTAS relative to control brain predominantly involved decreased abundance of proteins, with the greatest decreases observed for tenascin-C (TNC), cluster of differentiation 38 (CD38), and phosphoserine aminotransferase 1 (PSAT1); proteins typically increased in other neurodegenerative diseases. Proteins with the greatest increased abundance include potentially novel neurodegeneration-related proteins and small ubiquitin-like modifier 1/2 (SUMO1/2). The FMRpolyG peptide, proposed in models of FXTAS pathogenesis but only identified in trace amounts in the earlier study of FXTAS inclusions, was not identified in any of the FXTAS or control brains in the current study.Discussion: The observed proteomic shifts, while generally relatively modest, do show a bias toward decreased protein abundance with FXTAS. Such shifts in protein abundance also suggest altered RNA binding as well as loss of cell–cell adhesion/structural integrity. Unlike other neurodegenerative diseases, the proteome of end-stage FXTAS does not suggest a strong inflammation-mediated degenerative response.

scholarly journals Brain Atrophy and White Matter Damage Linked to Peripheral Bioenergetic Deficits in the Neurodegenerative Disease FXTAS

2021 ◽  
Vol 22 (17) ◽  
pp. 9171
Author(s):  
Junyi Wang ◽  
Eleonora Napoli ◽  
Kyoungmi Kim ◽  
Yingratana A. McLennan ◽  
Randi J. Hagerman ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Volume ◽  
Neurodegenerative Disorder ◽  
Fragile X ◽  
Mitochondrial Bioenergetics ◽  
Mri Findings ◽  
Mitochondrial Mass ◽  
Atp Production ◽  
Age Dependent ◽  
Ataxia Syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting subjects (premutation carriers) with a 55-200 CGG-trinucleotide expansion in the 5′UTR of the fragile X mental retardation 1 gene (FMR1) typically after age 50. As both the presence of white matter hyperintensities (WMHs) and atrophied gray matter on magnetic resonance imaging (MRI) are linked to age-dependent decline in cognition, here we tested whether MRI outcomes (WMH volume (WMHV) and brain volume) were correlated with mitochondrial bioenergetics from peripheral blood monocytic cells in 87 carriers with and without FXTAS. As a parameter assessing cumulative damage, WMHV was correlated to both FXTAS stages and age, and brain volume discriminated between carriers and non-carriers. Similarly, mitochondrial mass and ATP production showed an age-dependent decline across all participants, but in contrast to WMHV, only FADH2-linked ATP production was significantly reduced in carriers vs. non-carriers. In carriers, WMHV negatively correlated with ATP production sustained by glucose-glutamine and FADH2-linked substrates, whereas brain volume was positively associated with the latter and mitochondrial mass. The observed correlations between peripheral mitochondrial bioenergetics and MRI findings—and the lack of correlations with FXTAS diagnosis/stages—may stem from early brain bioenergetic deficits even before overt FXTAS symptoms and/or imaging findings.

Sign in / Sign up

Export Citation Format

Share Document