Broadened Friedreich's ataxia phenotype after gene cloning: Minimal GAA expansion causes late-onset spastic ataxia

Neurology ◽  
1997 ◽  
Vol 49 (6) ◽  
pp. 1617-1620 ◽  
Author(s):  
M. Ragno ◽  
G. De Michele ◽  
F. Cavalcanti ◽  
L. Pianese ◽  
A. Monticelli ◽  
...  
Keyword(s):  
Gene Cloning ◽  
Late Onset ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Spastic Ataxia ◽  
Gaa Expansion

Very late onset Friedreich's ataxia without cardiomyopathy is associated with limited GAA expansion in the X25 gene

Neurology ◽  
1997 ◽  
Vol 49 (4) ◽  
pp. 1153-1155 ◽  
Author(s):  
C. Gellera ◽  
D. Pareyson ◽  
B. Castellotti ◽  
F. Mazzucchelli ◽  
B. Zappacosta ◽  
...  
Keyword(s):  
Late Onset ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Gaa Expansion

scholarly journals Friedreich's Ataxia Frequency in a Large Cohort of Genetically Undetermined Ataxia Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexander F. Brown ◽  
Michael H. Parkinson ◽  
Hector Garcia-Moreno ◽  
Ese Mudanohwo ◽  
Robyn Labrum ◽  
...  
Keyword(s):  
Late Onset ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Diagnostic Process ◽  
Spinocerebellar Ataxias ◽  
Screening Process ◽  
Group A ◽  
Improve Patient Management ◽  
Group B ◽  
Testing Group

Background: Patients with suspected genetic ataxia are often tested for Friedreich's ataxia (FRDA) and/or a variety of spinocerebellar ataxias (SCAs). FRDA can present with atypical, late-onset forms and so may be missed in the diagnostic process. We aimed to determine FRDA-positive subjects among two cohorts of patients referred to a specialist ataxia centre either for FRDA or SCA testing to determine the proportion of FRDA cases missed in the diagnostic screening process.Methods: 2000 SCA-negative ataxia patients, not previously referred for FRDA testing (group A), were tested for FRDA expansions and mutations. This group was compared with 1768 ataxia patients who had been previously referred for FRDA testing (group B) and were therefore more likely to have a typical presentation. The phenotypes of positive cases were assessed through review of the clinical case notes.Results: Three patients (0.2%) in group A had the FRDA expansion on both alleles, compared with 207 patients (11.7%) in group B. The heterozygous carrier rate across both cohorts was of 41 out of 3,768 cases (1.1%). The size of the expansions in the three FRDA-positive cases in group A was small, and their presentation atypical with late-onset.Conclusions: This study demonstrates that FRDA is very rare among patients who were referred purely for SCA testing without the clinical suspicion of FRDA. Such cases should be referred to specialist ataxia centres for more extensive testing to improve patient management and outcomes.

scholarly journals Plasma Lipids and Lipoproteins in Friedreich's Ataxia and Familial Spastic Ataxia — Evidence for an Abnormal Composition of High Density Lipoproteins

1978 ◽  
Vol 5 (1) ◽  
pp. 149-156 ◽  
Author(s):  
Y. S. Huang ◽  
A. C. Nestruck ◽  
A. Barbeau ◽  
J. P. Bouchard ◽  
J. Davignon
Keyword(s):  
Plasma Lipids ◽  
Relative Proportion ◽  
Electrophoretic Pattern ◽  
Density Lipoprotein ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
High Density ◽  
High Density Lipoproteins ◽  
Spastic Ataxia ◽  
Lipids And Lipoproteins

SUMMARY:A systematic study of plasma lipids and lipoproteins was carried out in II cases of Friedreich's ataxia and 6 cases of familial spastic ataxia (Charlevoix-Saguenay disease) using II healthy normolipidemic volunteers of comparable age and sex as controls. No differences were noted in the fatty acid profile of the total lipid fraction, in the total cholesterol and phospholipids or in the percentage distribution of the individual phospholipid classes. The triglycerides were significantly higher in Friedreich's ataxia, but remained within the normal range. Although no systematic abnormalities could be detected in the electrophoretic pattern of plasma lipoproteins or in the apolipoprotein profile on polyacrylamide gel electrophoresis, major differences were found in the high density lipoprotein (HDL) fraction. Their total amount was reduced and their composition was abnormal in both neurological diseases. In Friedreich patients, the relative proportion of cholesterol and triglycerides was increased while the relative protein content was greatly reduced. In Charlevoix disease, a similar abnormality was seen except for the excess of triglycerides. The proportion of phospholipids in HDL was the same in the three groups of patients. In addition, the low density lipoprotein (LDL) fraction was slightly reduced in both diseases. This anomaly of the HDL fraction could indicate that the HDL apolipoprotein moiety has a greater affinity for cholesterol and triglycerides in Friedreich's ataxia than its normal counterpart.

Perturbation of precision grip in Friedreich's ataxia and late-onset cerebellar ataxia

1994 ◽  
Vol 9 (6) ◽  
pp. 650-654 ◽  
Author(s):  
Joachim Hermsdöourfer ◽  
Karl Wessel ◽  
Norbert Mai ◽  
Christian Marquardt
Keyword(s):  
Cerebellar Ataxia ◽  
Late Onset ◽  
Precision Grip ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia

scholarly journals Electromyography and Nerve Conduction Studies in Friedreich's Ataxia and Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)

1979 ◽  
Vol 6 (2) ◽  
pp. 185-189 ◽  
Author(s):  
J.P. Bouchard ◽  
A. Barbeau ◽  
R. Bouchard ◽  
R.W. Bouchard
Keyword(s):  
Nerve Conduction ◽  
Autosomal Recessive ◽  
Clinical Signs ◽  
Sensory Nerve ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Nerve Conduction Studies ◽  
Spastic Ataxia ◽  
Group I ◽  
Electrophysiological Studies

SummaryTwenty four ataxie patients were investigated with electromyography and nerve conduction studies. They were divided in two groups according to the area they came from, the evolution of the disease, and the clinical signs. Group I patients from the Rimouski area displayed all the clinical and electrophysiological signs of Friedreich's ataxia. Group II comprised patients who presented with a new syndrome known as the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Although the clinical evolution was better in the latter, there were more electromyographic signs of denervation and the motor conduction velocities were slower. Both groups showed identical and important abnormalities in sensory nerve conduction.The results of electrophysiological studies in spastic ataxia have not been reported to our knowledge. They underline the place of spastic ataxia as distinct f rom Friedreich's ataxia, spastic paraplegia, and the known familial neuropathies.

GAA expansion size and age at onset of Friedreich's ataxia

Neurology ◽  
2003 ◽  
Vol 61 (2) ◽  
pp. 274-275 ◽  
Author(s):  
I. Mateo ◽  
J. Llorca ◽  
V. Volpini ◽  
J. Corral ◽  
J. Berciano ◽  
...  
Keyword(s):  
Age At Onset ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Gaa Expansion

scholarly journals Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases

2001 ◽  
Vol 56 (5) ◽  
pp. 143-148 ◽  
Author(s):  
Lilian M. J. Albano ◽  
Mayana Zatz ◽  
A. Kim Chong ◽  
Débora Bertola ◽  
Sofia M. M. Sugayama ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Age Of Onset ◽  
Age At Onset ◽  
Cranial Nerves ◽  
Autosomal Recessive Inheritance ◽  
Molecular Study ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Gaa Expansion ◽  
Neurologic Findings

INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) - all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.

Sign in / Sign up

Export Citation Format

Share Document