Fatigue and body mass index in the Fragile X premutation carrier

Summers, Scott M.; Cogswell, Jennifer B.; Goodrich, John E; Mu, Yi; Nguyen, Danh V.; Brass, Steven D.; Hagerman, Randi J.

doi:10.1080/21641846.2014.881155

Cited by 10 publications

(12 citation statements)

References 38 publications

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“…Chronic fatigue is a common symptom of premutation carriers with and without FXTAS and it has a significant effect on their daily lives ( 85 , 86 ). It is likely associated with the mitochondrial dysfunction described previously in premutation carriers; previous studies have linked chronic fatigue in carriers with the severity of mitochondrial dysfunction ( 32 , 33 ).…”

Section: Chronic Fatiguementioning

confidence: 99%

“…Increased BMI is also thought to be indirectly related to fatigue because of its relation to sleep apnea, diabetes and coronary artery disease. Summers et al ( 85 ) reported that premutation carriers with FXTAS are more affected by fatigue than the individuals with premutation without FXTAS and the control group. Premutation carriers without FXTAS show an intermediate level between FXTAS patients and controls.…”

Section: Chronic Fatiguementioning

confidence: 99%

“…Premutation carriers without FXTAS show an intermediate level between FXTAS patients and controls. They mentioned that depression is correlated with fatigue and that treatment of depression reduces the fatigue scores of patients ( 85 , 88 ).…”

Section: Chronic Fatiguementioning

confidence: 99%

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Fragile X-Associated Neuropsychiatric Disorders (FXAND)

et al. 2018

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Fragile X syndrome (FXS) is caused by the full mutation (>200 CGG repeats) in the Fragile X Mental Retardation 1 (FMR1) gene. It is the most common inherited cause of intellectual disability (ID) and autism. This review focuses on neuropsychiatric disorders frequently experienced by premutation carriers with 55 to 200 CGG repeats and the pathophysiology involves elevated FMR1 mRNA levels, which is different from the absence or deficiency of fragile X mental retardation protein (FMRP) seen in FXS. Neuropsychiatric disorders are the most common problems associated with the premutation, and they affect approximately 50% of individuals with 55 to 200 CGG repeats in the FMR1 gene. Neuropsychiatric disorders in children with the premutation include anxiety, ADHD, social deficits, or autism spectrum disorders (ASD). In adults with the premutation, anxiety and depression are the most common problems, although obsessive compulsive disorder, ADHD, and substance abuse are also common. These problems are often exacerbated by chronic fatigue, chronic pain, fibromyalgia, autoimmune disorders and sleep problems, which are also associated with the premutation. Here we review the clinical studies, neuropathology and molecular underpinnings of RNA toxicity associated with the premutation. We also propose the name Fragile X-associated Neuropsychiatric Disorders (FXAND) in an effort to promote research and the use of fragile X DNA testing to enhance recognition and treatment for these disorders.

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Section: Chronic Fatiguementioning

confidence: 99%

Section: Chronic Fatiguementioning

confidence: 99%

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Fragile X-Associated Neuropsychiatric Disorders (FXAND)

et al. 2018

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“…Iron dysregulation has been linked to a series of neurodegenerative disease, including Parkinson and Alzheimer diseases, amyotrophic lateral sclerosis, restless legs syndrome, and prion diseases [21]. Indeed, Parkinsonism and dementia are common in those with FXTAS [7,22], and restless legs syndrome is more common in those with the premutation compared to controls [23]. …”

Section: Introductionmentioning

confidence: 99%

Dysregulated iron metabolism in the choroid plexus in fragile X-associated tremor/ataxia syndrome

et al. 2015

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Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene that is characterized by progressive action tremor, gait ataxia, and cognitive decline. Recent studies of mitochondrial dysfunction in FXTAS have suggested that iron dysregulation may be one component of disease pathogenesis. We tested the hypothesis that iron dysregulation is part of the pathogenic process in FXTAS. We analyzed postmortem choroid plexus from FXTAS and control subjects, and found that in FXTAS iron accumulated in the stroma, transferrin levels were decreased in the epithelial cells, and transferrin receptor 1 distribution was shifted from the basolateral membrane (control) to a predominantly intracellular location (FXTAS). In addition, ferroportin and ceruloplasmin were markedly decreased within the epithelial cells. These alterations have implications not only for understanding the pathophysiology of FXTAS, but also for the development of new clinical treatments that may incorporate selective iron chelation.

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“…Additional medical problems that are common in carriers, particularly aging carriers with neurological problems or FXTAS, include hypothyroidism (50% of females) [ 85 ], fibromyalgia (43% of females) [ 85 ], sleep apnea [ 86 ], migraine headaches [ 87 ], Restless Legs syndrome [ 88 ], fatigue [ 89 ] and hypertension [ 90 ]. Regular screening for hypothyroidism, hypertension, migraines, and sleep apnea are recommended because these problems also require treatment and can interfere with brain function if untreated.…”

Section: Expanding the Premutation Clinical Picturementioning

confidence: 99%

Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers

2014

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Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and it is characterized by a CGG expansion of more than 200 repeats in the FMR1 gene, leading to methylation of the promoter and gene silencing. The fragile X premutation, characterized by a 55 to 200 CGG repeat expansion, causes health problems and developmental difficulties in some, but not all, carriers. The premutation causes primary ovarian insufficiency in approximately 20% of females, psychiatric problems (including depression and/or anxiety) in approximately 50% of carriers and a neurodegenerative disorder, the fragile X-associated tremor ataxia syndrome (FXTAS), in approximately 40% of males and 16% of females later in life. Recent clinical studies in premutation carriers have expanded the health problems that may be seen. Advances in the molecular pathogenesis of the premutation have shown significant mitochondrial dysfunction and oxidative stress in neurons which may be amenable to treatment. Here we review the clinical problems of carriers and treatment recommendations.

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Fatigue and body mass index in the Fragile X premutation carrier

Cited by 10 publications

References 38 publications

Fragile X-Associated Neuropsychiatric Disorders (FXAND)

Fragile X-Associated Neuropsychiatric Disorders (FXAND)

Dysregulated iron metabolism in the choroid plexus in fragile X-associated tremor/ataxia syndrome

Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers

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