Friedreich ataxia today—preparing for the final battle

Michele, Giuseppe De; Filla, Alessandro

doi:10.1038/nrneurol.2015.33

Cited by 6 publications

(5 citation statements)

References 9 publications

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“…However, identification of the causal gene led to identification of a significant number of patients with late onset, they tend to have slower progression with less severe phenotype and are associated with smaller GAA expansions 10 . This shorter expansion enables residual Fxn expression 11 , thus modifying the classical FDRA phenotype, consistent with other data indicating that Fxn deficiency is directly related to the FRDA phenotype 12 . Extra-neurologic symptoms including metabolic dysfunction and insulin intolerance are observed in the majority and frank type I diabetes is observed in approximately 15% of patients, the severity of which is related to increasing repeat length [13][14][15] .…”

Section: Introductionsupporting

confidence: 91%

Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

Chandran

Gao

Swarup

et al. 2017

Preprint

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Section: Introductionsupporting

confidence: 91%

Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

Chandran

Gao

Swarup

et al. 2017

Preprint

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“…In addition, the dipstick assay measures the frataxin 81–210 isoform, but several isoforms of frataxin exist in different cells [ 59 ], with different biochemical and functional properties. Thus, it has been suggested that an expression of isoform ratios between patients and healthy individuals may be an even better surrogate outcome marker in the future [ 60 ]. Despite all these limitations, a clear correlation between frataxin levels in whole blood and clinical ataxia severity, as well as age at onset and GAA1 repeat size, could be confirmed, with age at onset being the strongest predictor of frataxin level.…”

Section: Discussionmentioning

confidence: 99%

Friedreich ataxia in Norway – an epidemiological, molecular and clinical study

Wedding

Kroken

Henriksen

et al. 2015

Orphanet J Rare Dis

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BackgroundFriedreich ataxia is an autosomal recessive hereditary spinocerebellar disorder, characterized by progressive limb and gait ataxia due to proprioceptive loss, often complicated by cardiomyopathy, diabetes and skeletal deformities. Friedreich ataxia is the most common hereditary ataxia, with a reported prevalence of 1:20 000 – 1:50 000 in Central Europe. Previous reports from south Norway have found a prevalence varying from 1:100 000 – 1:1 350 000; no studies are previously done in the rest of the country.MethodsIn this cross-sectional study, Friedreich ataxia patients were identified through colleagues in neurological, pediatric and genetic departments, hospital archives searches, patients’ associations, and National Centre for Rare Disorders. All included patients, carriers and controls were investigated clinically and molecularly with genotype characterization including size determination of GAA repeat expansions and frataxin measurements. 1376 healthy blood donors were tested for GAA repeat expansion for carrier frequency analysis.ResultsTwenty-nine Friedreich ataxia patients were identified in Norway, of which 23 were ethnic Norwegian, corresponding to a prevalence of 1:176 000 and 1:191 000, respectively. The highest prevalence was seen in the north. Carrier frequency of 1:196 (95 % CI = [1:752–1:112]) was found. Homozygous GAA repeat expansions in the FXN gene were found in 27/29, while two patients were compound heterozygous with c.467 T < C, L157P and the deletion (g.120032_122808del) including exon 5a. Two additional patients were heterozygous for GAA repeat expansions only. Significant differences in the level of frataxin were found between the included patients (N = 27), carriers (N = 37) and controls (N = 27).ConclusionsIn this first thorough study of a complete national cohort of Friedreich ataxia patients, and first nation-wide study of Friedreich ataxia in Norway, the prevalence of Friedreich ataxia in Norway is lower than in Central Europe, but higher than in the last Norwegian report, and as expected from migration studies. A south–north prevalence gradient is present. Based on Hardy Weinberg’s equilibrium, the carrier frequency of 1:196 is consistent with the observed prevalence. All genotypes, and typical and atypical phenotypes were present in the Norwegian population. The patients were phenotypically similar to European cohorts. Frataxin was useful in the diagnostic work-up of heterozygous symptomatic cases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0328-4) contains supplementary material, which is available to authorized users.

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“…The common theme of these movements is to focus on timing and accuracy using repetitive movements or tasks that require accuracy. The ability to maintain a stable posture is also examined directly (in the case of axial function) or indirectly (where movements at more distal joints require a more proximal 7 joints to provide a stable platform -e.g., accurate pointing of the finger at a target requires coordinated contraction of the muscles that stabilize the shoulder joint). The nervous system is constantly correcting and adjusting posture, and in CA errors in the timing and accuracy of these corrections results in increased sway and irregular gait and balance.…”

Section: ML In Assessing Ataxic Movementmentioning

confidence: 99%

“…For instance, research in PD showed the high frequency (3 Hz to 8 Hz) components of leg movements during Freezing of Gait (FOG) were not present in ordinary walking or standing. By calculating a power ratio of the "freeze" band [3][4][5][6][7][8] to the "locomotor" band [0.5-3 Hz], the authors could estimate a threshold to identify FOG events [194]. With a similar method, Handojoseno et al proved the power spectral density and wavelet energy of electroencephalography (EEG) could function as promising biomarkers to indicate FOG with 80% accuracy [195].…”

Section: Challenges and Future Prospectsmentioning

confidence: 99%

“…Otherwise, there is a very real risk of overlooking genuinely effective treatments or having unnecessarily large, protracted and therefore costly clinical trials to overcome the noise of less sensitive or inconsistent measurements [4], [6]. Third, some ataxias (e.g., those associated with multiple sclerosis) already have treatment but their efficacy in certain individuals is difficult to assess without accurate measurement [7]. In other ataxias there is active research with the prospect of new and emerging therapies whose success may depend critically on accurate measurement to identify any beneficial effect.…”

Section: Introductionmentioning

confidence: 99%

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Technological Evolution in the Instrumentation of Ataxia Severity Measurement

et al. 2023

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Cerebellar ataxia is the poorly coordinated movement that results from injury or disease affecting the cerebellum. The diagnosis and assessment of ataxia are significantly challenging due to dependency on clinicians' experience and the attendant subjectivity of such a process. In recent years, neuroimaging and sensor-based approaches, supported by effective machine learning techniques have made advances in the pursuit of addressing these clinical challenges. In this work, we present an outline of approaches to applying machine learning to this clinical challenge. We first provide a fundamental clinical overview with practical problems and then from a machine learning perspective, outline possible approaches with which to address these clinical challenges. Also discussed are the limitations in existing methods, the provision of cross disciplinary approaches and the current state-of-the-art as a potential basis for future research.

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Friedreich ataxia today—preparing for the final battle

Cited by 6 publications

References 9 publications

Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

Friedreich ataxia in Norway – an epidemiological, molecular and clinical study

Technological Evolution in the Instrumentation of Ataxia Severity Measurement

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