Friedreich's ataxia (FDRA) is the most common inherited ataxia worldwide, caused by homozygous GAA expansions in the FXN gene. Patients usually have early onset ataxia, areflexia, Babinski sign, scoliosis and pes cavus, but at least 25 % of cases have atypical phenotypes. Disease begins after the age of 25 in occasional patients (late-onset Friedreich ataxia (LOFA)). Little is known about the frequency and clinical profile of LOFA patients. One hundred six patients with molecular confirmation of FDRA and followed in three Brazilian outpatient centers were enrolled. General demographics, GAA expansion size, age at onset, cardiac, endocrine, and skeletal manifestations were evaluated and compared between LOFA and classic FDRA (cFDRA) groups. We used Mann-Whitney and Fisher tests to compare means and proportions between groups; p values <0.05 were considered significant. LOFA accounted for 17 % (18/106) and cFDRA for 83 % (88/106) of the patients. There were 13 and 48 women in each group, respectively. LOFA patients were significantly older and had smaller GAA expansions. Clinically, LOFA group had a tendency toward lower frequency of diabetes/impaired glucose tolerance (5.8 vs. 17 %, p = 0.29) and cardiomyopathy (16.6 vs. 28.4 %, p = 0.38). Skeletal abnormalities were significantly less frequent in LOFA (scoliosis 22 vs. 61 %, p = 0.003, and pes cavus 22 vs.75 %, p < 0.001) as were spasticity and sustained reflexes, found in 22 % of LOFA patients but in none of the cFDRA patients (p = 0.001). LOFA accounts for 17 % of Brazilian FDRA patients evaluated herein. Clinically, orthopedic features and spasticity with retained reflexes are helpful tips to differentiate LOFA from cFDRA patients.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s12311-015-0755-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recurrent DNA nicks drive massive expansions of (GAA) repeats.
Proc Natl Acad Sci U S A
December 2024
Department of Biology, Tufts University, Medford, MA 02155.
Article Synopsis
- Over 50 hereditary degenerative disorders are linked to the expansion of short tandem DNA repeats (STRs), especially (GAA) repeats, which are associated with diseases like Friedreich's ataxia.
- Researchers used a CRISPR-Cas9 nickase system to study the impact of introducing targeted DNA nicks near (GAA) repeats, discovering that nicks 5' of the repeat significantly boosted expansion rates and sizes in dividing cells.
- The study suggests that nicks can convert to double-strand breaks during DNA replication, resulting in repeat expansions, and also showed that 5' nicks can enhance expansion frequency in nondividing yeast cells, though less than in dividing cells.
Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters.
Int J Mol Sci
October 2024
Division of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Development (ENEA), 00123 Rome, Italy.
Friedreich ataxia (FRDA) is the most common inherited ataxia, primarily impacting the nervous system and the heart. It is characterized by GAA repeat expansion in the FXN gene, leading to reduced mitochondrial frataxin levels. Previously, we described a family displaying two expanded GAA alleles, not only in the proband affected by late-onset FRDA but also in the younger asymptomatic sister.
View Article and Find Full Text PDFBilateral Dentate Nuclei Hyperintensities and Response to 4-Aminopyridine in a Patient With Childhood-Onset GAA--Related Ataxia.
Neurol Genet
December 2024
From the Department of Brain and Behavioural Sciences (P.M., A.P., C.T., M.A.), University of Pavia; IRCCS Mondino Foundation (E.V., R.Z., I.P., S.G., S.R.A., C.T., E.M.V., M.A.), Pavia, Italy; Department of Neurology and Neurosurgery (M.-J.D.), Montreal Neurological Hospital and Institute, McGill University, Quebec, Canada; Advanced Imaging Center and Artificial Intelligence (S.N., A.P.), Department of Neuroradiology, IRCCS Mondino Foundation; and Department of Molecular Medicine (E.M.V.), University of Pavia, Italy.
Objectives: To report a novel imaging finding of bilateral dentate nuclei hyperintensities in a case of childhood-onset GAA--related ataxia (spinocerebellar ataxia 27B, SCA27B) and response to 4-aminopyridine (4-AP).
Methods: A 53-year-old woman with unsolved progressive cerebellar ataxia of childhood onset underwent clinical and imaging assessment and extensive genetic investigation.
Results: After excluding Friedreich ataxia, most common spinocerebellar ataxia-related expansions, and pathogenic variants in ataxia-related genes through exome sequencing, targeted long-range PCR and repeat-primed PCR analysis revealed a heterozygous pathogenic (GAA) expansion in Brain MRI showed bilateral dentate nuclei hyperintensities and peridentate white matter degeneration, a feature never reported before in SCA27B.
Clinical outcome assessments of disease burden and progression in late-onset GM2 gangliosidoses.
Mol Genet Metab
July 2024
NTSAD Association, Brookline, MA, USA; Gerald Cox Rare Care Consulting, LLC, Needham, MA, USA.
Article Synopsis
- Late-onset GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are rare and progressive neurogenetic disorders marked by symptoms like muscle weakness, balance issues, and speech difficulties.
- A study was conducted to understand the progression of these diseases using various clinical assessments, as there are currently no validated tools specifically for late-onset GM2 gangliosidoses.
- Results showed that patients experienced significant neurological deterioration over time, with worsening scores indicating a correlation between the length of time since diagnosis and declining function in coordination and speech.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!