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|LETTER TO EDITOR
|Year : 2017 | Volume
| Issue : 5 | Page : 1153-1155
Spinocerebellar ataxia type 2 associated with amyotrophic lateral sclerosis
Rajesh K Singh, Kamlesh K Sonkar, Sanjeev Bhoi, Jayantee Kalita, Ushakant Misra
Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Web Publication||6-Sep-2017|
Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow - 226 014, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Singh RK, Sonkar KK, Bhoi S, Kalita J, Misra U. Spinocerebellar ataxia type 2 associated with amyotrophic lateral sclerosis. Neurol India 2017;65:1153-5
Coexistence of spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis (ALS) is rare. We report a patient with SCA 2 who developed ALS.
A 59-year old man had progressive imbalance and dysarthria for 10 years, and six years later, he developed progressive quadriparesis, pseudobulbar affect and bulbar weakness. He was diabetic for 22 years, and his brother had SCA-2. The patient had bilateral ptosis, fasciculations, wasting of hand and tongue, mild quadriparesis and bilateral cerebellar signs [Figure 1]a and [Figure 1]b. Blood counts, hemoglobin and serum chemistry were normal. The electrodiagnostic study was consistent with ALS. Cranial magnetic resonance imaging (MRI) revealed cerebellar atrophy [Figure 1]c. Genetic analysis was consistent with SCA-2 (ATXN2 gene [gene coding for spinocerebellar ataxia type 2 protein, ataxin-2] approximately 22, 37 CAG [cytosine-adenine-guanine] repeats).
|Figure 1: (a) Wasting of hand muscles with clawing. (b) Tongue wasting. (c) Cerebellar atrophy|
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This patient is the 6th case of SCA-2 with ALS [Table 1]. Our patient was confirmed as SCA-2 by genetic testing, and ALS by clinical and electromyography (EMG) findings. The protein synthesized by ATXN2 is known as ataxin-2, which is involved in ribonucleic acid metabolism and translation regulation. In SCA-2, TAR DNA [trans-activation response element deoxyribonucleic acid] binding protein 43 (TDP-43) is abnormally localized in the brain. In ALS, ATXN2 is abnormally localized in the spinal cord neurons, suggesting a relationship between SCA-2 and ALS. In animal and cellular models, ATXN2 is a modifier of TDP-43 toxicity. CAG repeat expansion in ATXN2 can increase the pathological form of TDP-43 by enhancing C-terminal cleavage and phosphorylated TDP-43.
We searched the literature for an association between SCA-2 and motor neuron disease/ALS and found only five such cases .,,,, In a study by Elden et al.,ATXN2 intermediate-length polyglutamine expansions was associated with an increased risk for ALS. Intermediate (27-33) and full CAG expansion (>34) are rarely associated with ALS. It is unclear why pathologic expansion of >32 CAG repeats of ATXN2 gene leads to Parkinson's disease and ALS rarely with cerebellar ataxia. In the autopsy studies of SCA-2 patients, there is a neuronal loss in substantia nigra with relatively preserved striatum. This could account for the levodopa responsive Parkinsonian features in SCA-2. A morphometric analyses in 11 autopsies of SCA-2 revealed reduction of lumbar (33-83% of normal) and thoracic motor neurons (27-64%), but a definite correlation between SCA-2 and ALS could not be established. Toxic protein accumulation and its improper localisation may result in neuronal death and overlapping clinical features.
We thank Mr. Shakti Kumar for secretarial help.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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|[Pubmed] | [DOI]|