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Year : 2005  |  Volume : 53  |  Issue : 3  |  Page : 308-310

High prevalence of spinocerebellar ataxia type 1 in an ethnic Tamil community in India

1 Department of Neurology, Government Stanley Medical College and Hospital,chennai, India
2 Saha institute of Nuclear Physics, Kolkatta, India

Date of Acceptance30-Apr-2005

Correspondence Address:
M Dhanaraj
19, Panchaliamman koil street, Arumbakkam, Chennai – 600106
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.16929

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 » Abstract 

Objective: To study the prevalence, clinical and molecular genetic characteristics of cerebellar ataxia in an ethnic Tamil community in India. Methods: An epidemiological study of cerebellar ataxia was done in two villages in the Indian state of Tamilnadu where its prevalence was observed to be high. All the people were screened and the clinical characteristics of those with ataxia were recorded. Genetic analysis was done in those with ataxia and in two asymptomatic control groups - group I belonging to the affected community and group II belonging to the unaffected community. The clinical and genetic results are correlated. Measures to help the community are suggested. Results: The total population of the two villages was 378. Among them 345 belonged to Vanniyakula Kshatriyar community and 33 to another. Cerebellar ataxia was found in 25 individuals belonging only to the former community (7.2%). The mean age of onset was 39.8 years and the salient features were ataxic gait (100%), dysarthria (100%), pyramidal signs (72%), slow saccades (48%) and bleeding diathesis (12%). Genetic studies were done in 17 of the study group. All showed pathological expansion of CAG repeats above 40, in chromosome 6p, diagnostic of SCA1. 7 of the 18 in the control group (I) and none in control group (II) had CAG repeats above 40. Conclusion: The prevalence of SCA1 is high (7.2%) in this ethnic Tamil community with a large asymptomatic group waiting to manifest. The symptomatic individuals need social support and rehabilitation. Appropriate counseling, prenatal evaluation and therapy will prevent the spread of disease to the next generation.

Keywords: Clinical features; genetics; India; prevalence; SCA1.

How to cite this article:
Rengaraj R, Dhanaraj M, Arulmozhi T, Chattopadhyay B, Battacharyya N P. High prevalence of spinocerebellar ataxia type 1 in an ethnic Tamil community in India. Neurol India 2005;53:308-10

How to cite this URL:
Rengaraj R, Dhanaraj M, Arulmozhi T, Chattopadhyay B, Battacharyya N P. High prevalence of spinocerebellar ataxia type 1 in an ethnic Tamil community in India. Neurol India [serial online] 2005 [cited 2023 Jan 29];53:308-10. Available from: https://www.neurologyindia.com/text.asp?2005/53/3/308/16929

 » Introduction Top

Spinocerebellar ataxia type 1 (SCA1) is characterized by progressive cerebellar ataxia, dysarthia and eventual bulbar dysfunction with abnormal CAG trinucleotide repeat expansion of the SCA1 gene in chromosome locus 6p23.[1] In community-based studies the prevalence rate is 1 to 2 per 100,000 populations.[1] Most of the hospital-based studies in India showed SCA2 and SCA3 to be more common.[2],[3],[4],[5],[6] In this paper, we report a population-based study of SCA1 in an ethnic Tamil community inhabiting two small villages in the state of Tamilnadu.

 » Materials and methods Top

Rajapalayam (village 1) and Kottamedu (village 2) are two small adjacent villages near Vellore about 150 km from Chennai. Most of the people living here belong to the Vanniyakula Kshatriyar community. Agriculture is the main occupation. One patient from Rajapalayam reported to our department with progressive unsteady gait. Clinical and imaging studies confirmed degenerative ataxia. Genetic studies showed CAG repeats above 40 in chromosome 6p23 diagnostic of SCA1. He revealed that quite a few of his villagers have similar disorder. This prompted us to conduct the epidemiological survey in the above villages.

The survey team comprised two neurologists, two residents and five paramedical persons, who were adequately trained. The study was carried out between January and April 2004. A house-to-house survey was done in all the houses using standard proforma.[7] Neurological assessment was done in all the inhabitants of the two villages. Detailed examination was done in those who had ataxia and the findings were recorded. All the symptomatic individuals were given genetic counseling. Genetic testing was done in those symptomatic individuals who were willing. After informed written consent, 5ml of heparinized blood was taken and sent for analysis to Saha Institute of Nuclear Physics, Kolkata. For control, blood was taken from two groups of asymptomatic volunteers, (neither randomized nor blinded) group I, belonging to the same community, (IA-below 40 years of age, IB- above 40 years of age), group II belonging to a different community residing in the same village.

Genomic DNA isolation from heparinized blood samples was done by the standardized method. The method used to determine the CAG repeat number was essentially same as reported earlier using the PCR primer Rep1 and Rep2.[5] Genetic and clinical correlation was done at the end.

 » Results Top

The total population in both villages was 378; among them 345 belonged to the Vanniyakula Kshatriyar community and the remaining 33 to another single community. Among the 345, 180 were men and 165 women. The age-adjusted distribution of the population and symptomatic individuals is given in [Table - 1].

The mean age of onset of the illness was 39.8 years (range 23 - 57 years). The first symptom was unsteadiness on walking in 20(80%), slurring of speech in five (20%). Pyramidal signs were found in 18(72%), sensory neuropathy in seven (28%), cognitive decline in four (16%), slow saccades in 12(48%), deafness in two (8%), nystagmus in two (8%) and optic atrophy in one (4%). None had extra pyramidal involvement. Bleeding diathesis was noted in three (12%) of them in whom the exact cause could not be identified. MRI done in two patients showed cerebellar atrophy.

Genetic testing was done in 17 of the symptomatic group. All had CAG repeats above 40 (mean 43.6, range 40 - 48). Two of them were homozygous. The number of CAG repeats in symptomatic individuals and the age of onset of the illness are shown in [Table - 2]. The regression analysis showing inverse relationship between age of onset of ataxia and number of CAG repeats is shown in [Figure - 1]. The family pedigree of all those symptomatic individuals is given in [Figure - 2]. In the control group IA belonging to the affected community below 40 years of age six out of ten (60%), and in control group IB above 40 years of age one out of eight (12.5%) had CAG repeats above 40. In control group II, belonging to the different community, all had normal CAG repeats.

 » Discussion Top

In the published literature on spinocerebellar degeneration from India SCA1 was reported to be less common. In the pioneering study of Wadia all the 14 individuals had SCA2 and none SCA1.[2] Later in a study of 70 patients of degenerative ataxia by Ambar Chakravarthy only two were SCA1.[3] Ghosh has reported 3 cases and Basu 5 cases.[4],[5] However in a recent report from NIMHANS, Bangalore among 84 genetically tested ataxic individuals 15 belonged to SCA1.[6] These studies were hospital-based. In this present community based study SCA1 was found to be prevalent in 7.2% of the members of the Vanniyakula Kshatriyar community. Such a high prevalence has not been observed in any one of the previous studies. This is probably because all the members of the two villages have a common origin from a single family with the affected gene, consanguineous marriage and remaining in the same area for their livelihood.

This disorder was observed more in individuals between 41-50 years (18%) of age, comparable to other studies.[8] The presenting symptom was unsteady gait as in other studies.[9] Pyramidal signs were found in 18 (72%) in the later stages in contrast to previous reports.[10] Sensory neuropathy observed in 28% of the patients by five years of the disease duration was similar to the previous studies.[10] Four patients (16%) had cognitive decline correlating well with duration and severity of the disease as reported earlier.[11] Extrapyramidal signs in the form of tremors were observed in almost all cases by Won Yong Lee et. al.[12] But in the present series none had this manifestation. Bleeding diathesis in the form of profuse bleeding gums was seen in three patients (12%). The exact cause of it could not be identified, as none were willing for further investigations. From the available history bulbar dysfunction, aspiration and respiratory failure were the common endpoints in most of the patients. The mean age of death was around 55 years as reported by the elders of the village.

Earlier studies have shown the number of CAG repeats in SCA1 was between 39-91. In this present series it was between 40-48 (mean 43.6).[12] There were two symptomatic individuals with homozygous pathological CAG expansions but they did not differ from others in disease manifestation, severity and progression. Similar observation has already been reported by Ranum et. al.,[13] Previous studies have reported a correlation between the number of repeats and the severity of disease; the larger the repeat the earlier the onset and more severe the disease.[13] However in this series there was no definite correlation between the age of onset and the severity of illness with CAG repeats. Even though the regression analysis had shown an inverse relationship between numbers of CAG repeats and age of onset of ataxia it was not statistically significant ( P = 0.02). The sample is too small for it to be statistically significant.

Whereas all the normal persons (control group II) had CAG repeats less than 36, 60% of the unaffected volunteers in control group IA had CAG repeats above 40. This indicates a large number of asymptomatic young persons, who genotypically positive are likely to manifest the disease later. One (57-year old female) in control group1B with 41 repeats was asymptomatic. She may manifest still later, as the longest age of onset in our series was 57 years, or may remain asymptomatic as shown by Goldfarb et al, in whose study, a woman with 44 CAG repeats was asymptomatic even at an age of 66 years.[14]

The disease has affected the community to such an extent that the affected persons are unable to perform their work and dependent on others for the livelihood at middle age itself. The community can be helped by adequate support and rehabilitation of the symptomatic individuals by government and non-governmental organizations. Appropriate genetic counseling and prenatal testing will help to eliminate the disease in the coming generation.

 » References Top

1.Subramony SH Disorders of the cerebellum including the degenerative ataxias in Neurology in clinical practice, Ed by Bradley WG, Daroff RB, Fenichel GM, Jankovic J. 4th edition. Butter worth Heinemann.Philadelphia.2004;2169-84   Back to cited text no. 1    
2. Wadia NH, A clinicogenetic analysis of six Indian spinocerebellar ataxia (SCA2) pedigrees. The significance of slow saccades in diagnosis. Brain 1998;121:2341-55.  Back to cited text no. 2    
3.Basu P, Chattopadhyay B, Gangopadhaya PK, Analysis of CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7 and DRPLA loci in spinocerebellar ataxia patients and distribution of CAG repeats at the SCA1, SCA2 and SCA6 loci in nine ethnic populations of eastern India, Hum Genet., 2000;106;597-604.  Back to cited text no. 3    
4.Chakravarthy A, Mukherjee S C, Primary degenerative cerebellar ataxias in ethnic Bengalees in West Bengal: some observations. Neurology India2003; 51; 227-34  Back to cited text no. 4    
5.Ghosh B, Gangopafhyay PK, Saha S, Genetic study of adult onset inherited progressive ataxia. J Assoc Neuroscientists Eastern India 2000;5:51-4  Back to cited text no. 5    
6.Kumar S, Spinocerebellar Ataxias: From phenotype to genotype in National Neurosciences Conference Abstracts. NIMHANS, Bangalore: 2004;36-7  Back to cited text no. 6    
7.Gourie-Devi M, Gururaj G, Satishchandra P. Neuroepidemiology in developing Countries. Second edition. Prism books. Bangalore. 1997;81-98.  Back to cited text no. 7    
8.Zoghbi HY, Pollack MS, Lyons LA, Ferrell RE, Daiger SP, Beaudet AL Spinocerebellar ataxia: variable age of onset and linkage to human leukocyte antigen in a large kindred. Ann Neurol 1998; 23:580-4  Back to cited text no. 8    
9.Svetel M, Culjkovic B, Sternic N, Dragasovic B, Clinico - genetic study of type 1 spinocerebellar ataxia. Svp Arch Celok Lek: 1999: 127(5-6) 157-62  Back to cited text no. 9    
10.Sasaki H, Fakazawa T, Yanagihava T, Clinical features and natural history of spinocerebellar ataxia type 1. Acta. Neurol. Scan: 1996: 93(1): 64-71  Back to cited text no. 10    
11.Burk K, Globas C, Bosch S, Klockgether T, Zuhlke C, Daum I et. al., Cognitive deficits in spinocerebellar ataxia type 1,2 and 3. J Neurol 2003; 250: 207 - 11.  Back to cited text no. 11    
12.Lee WY, Jin DK, Oh MR., Lee JE, Song SM, Lee EA et. al. Frequency analysis and clinical characterization of spinocerebellar ataxia type 1,2,3,6 and 7 in Korean patients. Arch: Neurol: Volume 60 (6) 2003: 858-63.  Back to cited text no. 12    
13.Ranum LP, Chung MY, Banfi S, Bryer A, Schut LJ, Ramesar R et al, Molecular and clinical correlations in spinocerebellar ataxia type 1: evidence for familial effects on the age at onset. Am J Hum Genet 1994; 55:244-52.   Back to cited text no. 13    
14. Goldfarb LG, Vasconcelos O, Platonov FA, Lunkes A, Kipnis V, Kononova S et. al., Unstable triplet repeat and phenotypic variability of spino cerebellar ataxia type 1. Ann Neurol 1996;39:500-6.  Back to cited text no. 14    


[Figure - 1], [Figure - 2]


[Table - 1], [Table - 2]

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