| Article Access Statistics|
| Viewed||1140 |
| Printed||14 |
| Emailed||0 |
| PDF Downloaded||31 |
| Comments ||[Add] |
Click on image for details.
|LETTERS TO EDITOR
|Year : 2018 | Volume
| Issue : 1 | Page : 230-231
Sporadic spinocerebellar ataxia, type 5: First report from India
Rohan Mahale1, Anish Mehta1, Sridevi Hegde2, Kiran Buddaraju1, Mahendra Javali1, Purushottam T Acharya1, Rangasetty Srinivasa1
1 Department of Neurology, MS Ramaiah Medical College and Hospital, Bengaluru, Karnataka, India
2 Department of Medical Genetics, Manipal Hospitals, Bengaluru, Karnataka, India
|Date of Web Publication||11-Jan-2018|
Dr. Rohan Mahale
Department of Neurology, MS Ramaiah Medical College and Hospital, Bengaluru - 560 054, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Mahale R, Mehta A, Hegde S, Buddaraju K, Javali M, Acharya PT, Srinivasa R. Sporadic spinocerebellar ataxia, type 5: First report from India. Neurol India 2018;66:230-1
|How to cite this URL:|
Mahale R, Mehta A, Hegde S, Buddaraju K, Javali M, Acharya PT, Srinivasa R. Sporadic spinocerebellar ataxia, type 5: First report from India. Neurol India [serial online] 2018 [cited 2019 Apr 23];66:230-1. Available from: http://www.neurologyindia.com/text.asp?2018/66/1/230/222857
Spinocerebellar ataxia (SCA) is a form of hereditary neurodegenerative ataxia. SCA presents with the autosomal dominant cerebellar ataxia (ADCA) phenotype. Harding proposed the classification of ADCA into Type I, Type II, and Type III based on the clinical phenotypes. ADCA type I presents with both cerebellar and noncerebellar signs. ADCA Type I includes SCA1–SCA4, SCA8, SCA10, SCA12–SCA23, SCA25, SCA27, SCA28, and SCA32–SCA36. ADCA Type II consists of syndromes in association with pigmentary maculopathies and includes SCA7. ADCA Type III includes mostly pure cerebellar syndromes and includes SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. However, noncerebellar signs such as mild neuropathy, pyramidal signs, and Parkinsonism More Details are seen in a small proportion of patients with ADCA type III. SCA6 is the most common subtype of ADCA Type III. The prevalence of SCA5 has been reported to be relatively rare. There is no genetically proven case of SCA5 from the Indian subcontinent. Hereby, we report the case of a 26-year old man, who presented with gradually progressive gait ataxia with cognitive impairment. Magnetic resonance imaging (MRI) of the brain showed pontocerebellar and diffuse cerebral atrophy. Genetic analysis revealed mutation in the SPTBN2 gene which is associated with SCA5.
A 26-year old man, born out of nonconsanguineous parentage, with normal perinatal and developmental history, presented with a decline in scholastic performance since he was 14 years of age. He also had unsteadiness of gait of 11 years, and slurring of speech of 9 years duration. The initial symptom noticed by parents was the decline in his scholastic performance. He was good at his studies till he was 14 years of age, when he started having a decline in his scholastic performance at school and was unable to clear his examination. They also noticed unsteadiness in his gait as he used to sway towards either side for the last 11 years. He used to fall while walking on uneven surfaces. The unsteadiness of gait was slowly progressive, and he was still self-ambulant at the time of evaluation. He had slurring of speech in the form of mild separation of syllables for the last 9 years. There was no upper limb incoordination, visual, hearing or swallowing difficulty, weakness or sensory symptoms in the limbs. He did not have myoclonus or any other type of seizures. None of the family members had similar complaints. He did not have other comorbidities. Systemic examination was unremarkable. On neurological examination, he had hammer toes. His mini-mental state score was 18/30. Mental state examination showed diffuse cerebral involvement. His speech was slurred and of scanning quality. The cranial nerve examination was normal. The fundus examination was normal. Motor examination showed hypotonic limbs with hyporeflexia and a normal power. Sensory examination showed distal hypoesthesia of the lower limbs to touch and pain till the lower one-third of the legs. There was mild incoordination of both upper limbs with prominent gait ataxia. Plantar responses were flexor. Complete hemogram, renal, thyroid, and liver function tests were normal. Fasting lipid profile and creatinine phosphokinase levels were normal. Vitamin B12 and E and folate levels were normal. Serological tests for human immunodeficiency virus and venereal disease research laboratory testing were nonreactive. Brain magnetic resonance imaging (MRI) showed a pontocerebellar and diffuse cerebral atrophy [Figure 1]. Nerve conduction studies (NCS) were suggestive of sensory neuropathy of both lower limbs. He was evaluated prior to the present admission. Genetic analysis for Freidriech's ataxia (FA), SCA 1, 2, 3, and 6, and dentatorubropallidoluysian atrophy was negative. Plasma lactate was normal. A detailed genetic analysis of approximately 900 genes was done. Mutation in the SPTBN2 gene was noted, which is associated with SCA5.
|Figure 1: Brain MRI fluid-attenuated inversion recovery (FLAIR) images axial view (a) showing cerebellar atrophy (white arrow), pontine and peduncular atrophy (red arrow) as well as (b) cerebellar atrophy (white arrow) and (c) cerebral atrophy (white arrow); (d) sagittal T1 wieghted MRI also shows a pontocerebellar atrophy (red arrow)|
Click here to view
Ataxia (impaired coordination) in adults can be a genetic or acquired disorder. In patients with hereditary degenerative ataxias, the initial symptoms are gait imbalance followed by appendicular ataxia and cerebellar dysarthria. SCAs are hereditary degenerative progressive autosomal dominant ataxias characterized by degeneration of cerebellum and brainstem. SCA5 belongs to ADCA type III phenotype. SCA5 is a rare form of slowly progressive dominant cerebellar ataxia referred to as “Lincoln family ataxia.” The gene implicated in the causation of SCA5 is spectrin, beta-3, non-erythrocyte 2 (SPTBN2)., Spectrins are the scaffolding proteins forming important structural components of the plasma membrane skeleton. This protein helps in maintaining shape, organization, and integrity of plasma membrane. They also help in transport of cellular organelles and in assembling specialized membrane domains. SPTBN2 gene encodes a β3-spectrin with high expression in Purkinje cells, which is involved in excitatory glutamate signalling through stabilization of the glutamate transporter, excitatory amino acid transporter 4 (EAAT4), at the surface of the membrane. Deficiency of β3-spectrin in the cerebellar Purkinje cells causes cell loss and cerebellar atrophy with thinning of the molecular layer.
Three families (American, German and French) with SCA5 have been reported so far., The age of onset of symptoms ranges from 10 to 68 years, with a mean of 33 years. Patients have age-related penetrance without anticipation. They present with cerebellar ataxia, oculomotor abnormalities such as gaze-evoked nystagmus, downbeat nystagmus, and impaired smooth pursuit. Other noncerebellar signs such as facial myokimia, horizontal gaze palsy, intention or resting tremor, brisk deep tendon reflexes, and impaired proprioception have been reported. Brain MRI shows diffuse atrophy of the cerebellum without any involvement of the brainstem or any other brain regions.
Our patient had symptom onset at the age of 14 years. The characteristic symptoms were impaired cognition, cerebellar ataxia, and dysarthria. There were no symptomatic family members. Brain MRI showed pontocerebellar atrophy with diffuse cerebral atrophy. NCS showed sensory neuropathy of both lower limbs. Genetic analysis showed mutation of SPTBN2 gene, which is commonly associated with SCA5. As both the parents were healthy, SPTBN2 gene mutation in this patient may have been a de novo mutation.
This is the first report of genetically-proven sporadic SCA5 from the Indian subcontinent. In patients presenting with symmetrical cerebellar signs, impaired cognition, and sensory neuropathy with the brain MRI showing pontocerebellar and cerebral atrophy, a possibility of SCA5 should be considered, after the more common degenerative diseases, FA as well as SCA1, 2 and 3 have been ruled out.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Taroni F, DiDonato S. Pathways to motor incoordination: The inherited ataxias. Nat Rev Neurosci 2004;5:641-55.
Harding AE. Classification of the hereditary ataxias and paraplegias. Lancet 1983;1:1151-5.
Schols L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomal dominant cerebellar ataxias: Clinical features, genetics, and pathogenesis. Lancet Neurol 2004;3:291-304.
Fujioka S, Sundal C, Wszolek ZK. Autosomal dominant cerebellar ataxia type III: A review of the phenotypic and genotypic characteristics. Orphanet J Rare Dis 2013;8:14.
Ranum LP, Schut LJ, Lundgren JK, Orr HT, Livingston DM. Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11. Nat Genet 1994;8:280-4.
Ikeda Y, Dick KA, Weatherspoon MR, Gincel D, Armbrust KR, Dalton JC, et al
. Spectrin mutations cause spinocerebellar ataxia type 5. Nature Genet 2006;38:184-90.
Cho E, Fogel BL. A family with spinocerebellar ataxia type 5 found to have a novel missense mutation within a SPTBN2 spectrin repeat. Cerebellum 2012;12:162-4.
Elsayed SM, Heller R, Thoenes M, Zaki MS, Swan D, Elsobky E, et al
. Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2
mutatons. European J Med Genet 2014;22:286-8.
Perkins EM, Clarkson YL, Sabatier N, Longhurst DM, Millward CP, Jack J, et al
. Loss of beta-III spectrin leads to Purkinje cell dysfunction recapitulating the behavior and neuropathology of spinocerebellar ataxia type 5 in humans. J Neurosci 2010;30:4857-67.
Burk K, Zuhlke C, Konig IR, Ziegler A, Schwinger E, Globas C, et al
. Spinocerebellar ataxia type 5: Clinical and molecular genetic features of German kindred. Neurology 2004;62:327-9.
Stevanin G, Herman A, Brice A, Durr A. Clinical and MRI findings in spinocerebellar ataxia type 5. Neurology 1999;53:1355-7.