Spinocerebellar ataxias types 1, 2 and 3: age adjusted clinical severity of disease at presentation correlates with size of CAG repeat lengths.
OBJECTIVE
The objective of this study was to determine the correlation, if any, between the clinical rate of disease progression at presentation with the CAG repeat size in patients with spinocerebellar ataxias 1, 2 and 3 (SCA1, SCA2 and SCA3).


METHODS
The severity of ataxia was measured using the International Cooperative Ataxia Rating Scale (IARS) in 31 patients of SCA1 (mean+/-SD age: 35.1+/-12.6 years; age at onset (AAO): 29.9+/-10.7 years), 25 patients of SCA2 (age: 34.9+/-14.9 years; AAO: 29.7+/-14.0 years) and 15 patients of SCA3 (age: 40.9+/-8.6 years; AAO: 36.9+/-10.1). The rate of disease progression at presentation was measured by the age adjusted IARS (IARS/Age). For each SCA, correlations of AAO, raw scores of IARS, age adjusted IARS and duration adjusted IARS (IARS/Duration) with the CAG repeat size were determined.


RESULTS
The number of CAG repeats of the abnormal allele ranged from 42 to 67 in SCA1, 38 to 66 in SCA2, and 69 to 79 in SCA3. In all the three types of SCAs, there were significant inverse correlations of AAO with CAG repeat size (SCA1: r=-0.9, p<0.0001; SCA2: r=-0.7, p<0.0001; SCA3:-0.8, p=0.0003) and significant positive correlations of IARS/Age with CAG repeat size (SCA1: r=0.6, p=0.0015; SCA2: r=0.9, p<0.0001; SCA3:0.7, p=0.0057). However, the raw IARS scores and the duration adjusted IARS scores did not correlate significantly with the CAG repeat sizes.


CONCLUSIONS
These data suggest that the rate of clinical disease progression at presentation, especially in SCA2, is dependent on the CAG repeat size, and may commence linearly from birth.
Netravathi
M
M
Department of Neurology, National Institute of Mental Health & Neurosciences, Bangalore-560029, India.
Pal
Pramod Kumar
PK
Purushottam
Meera
M
Thennarasu
Kandavel
K
Mukherjee
Mitali
M
Jain
Sanjeev
S
D000328:Adult; D000367:Age Factors; D000067696:Ataxin-1; D000067699:Ataxin-3; D000067528:Ataxins; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000503:physiopathology; D018911:Trinucleotide Repeats / Q000235:genetics*
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3