Year : 2020 | Volume
: 3 | Issue : 1 | Page : 1--2
Ataxia telangiectasia in India—Identifying the hidden glacier
Rukmini M Kandadai, Rupam Borgohain
Department of Neurology, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
Dr. Rukmini M Kandadai
Department of Neurology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad 500028, Telangana.
|How to cite this article:|
Kandadai RM, Borgohain R. Ataxia telangiectasia in India—Identifying the hidden glacier.Ann Mov Disord 2020;3:1-2
|How to cite this URL:|
Kandadai RM, Borgohain R. Ataxia telangiectasia in India—Identifying the hidden glacier. Ann Mov Disord [serial online] 2020 [cited 2022 Aug 10 ];3:1-2
Available from: https://www.aomd.in/text.asp?2020/3/1/1/281744
Ataxia telangiectasia (AT) is an autosomal-recessive disorder caused by mutation in the ATM (ataxia telangiectasia mutated) gene. Manifesting usually as a progressive neurodegenerative disease, it is a multisystem disorder characterized by oculocutaneous telangiectasias as well as the predilection to recurrent infections as well as malignancies.
It was first described by Syllaba and Henner in three adolescent Czech siblings in 1926, but was named Louis Bar syndrome till the 1960s, based on the publications of Louis Bar in 1941. Boder and Sedgwick gave the disease its name AT in 1957.
The clinical features were compiled based on a list of 101 patients with AT by Boder and Sedgwick in 1963 (cerebellar ataxia and oculocutaneous telangiectasia being inclusion criteria). The disease starts in the first few years usually in the first decade, with progressive cerebellar ataxia, oculomotor apraxia, and progressive cognitive impairment. Sensorimotor axonal neuropathy occurs concomitantly worsening the balance problems. Extrapyramidal manifestations, including dystonia, myoclonus, choreoathetosis, Parkinsonism, and tremor, are common manifestations. Systemic manifestations of oculocutaneous telangiectasias, frequent sinopulmonary infections as well as malignancies are common feature of the classical manifestations of AT.
The lymphocytic deficiency and reduction in immunoglobulin deficiency were identified in 1950s, whereas elevated alpha-fetoprotein was described by Waldmann et al. in 1972. The gene for AT was mapped to the long arm of chromosome 11 (11q22-23) by Gatti et al. in 1988. In 1995, an international consortium led by Shiloh and Collins identified the defective gene responsible for AT (ATM).ATM gene is ubiquitous and has a deoxyribonucleic acid (DNA) repair/check point region as well as a protein kinase region and has a major role in surveillance of DNA damage.
The availability of genetic testing has increased the phenomenological spectrum of AT and variant forms of patients with milder disease without cerebellar ataxia or telangiectasias have been described. There are more than 500 unique mutations with a significant heterogeneity at the clinical and cellular levels but the final underlying pathogenesis is reduction or absence of ATM protein. Although the disease is an autosomal recessive and is manifested in those with two abnormal alleles, an increased prevalence of malignancies especially breast cancer has been identified in those with single allele (carriers).
Currently, there are no treatment options available to target the disease. Management is symptomatic. Infections are major cause of mortality and early identification with early antibiotics usage is required. Immunizations and regular immunoglobulin infusions have been tried. Regular surveillance for malignancies is recommended. But lots of avenues are being investigated for possible therapeutic effect. Newer techniques such as dexamethasone encapsulated in erythrocytes (EryDex System) can release dexamethasone for 1 month and may be effective. Gene therapy for improving reading through the mutated gene has been tried out with various new molecules but is yet to yield results.
In this article, Manjunath et al., have published a large series of 100 patients with AT. This is the first comprehensive compilation of Indian patients with AT; this cohort had a mean age of symptom manifestation at 3.9 ± 2.84 years. Mean disease duration was 4.81 ± 3.30 years and clinical manifestations were similar to those observed worldwide (this study). The percentage of consanguinity was 60% among this population, a unique manifestation of the cultural and social practices commonly seen in South India. This study brings out the dire need to have a database of Indian patients with AT given the high prevalence of inbreeding and large population. Genotyping these patients and long-term follow-up can help us in formulating therapies and investigating newer modalities.
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Conflicts of interest
There are no conflicts of interest.
|1||Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM. Ataxia telangiectasia: A review. Orphanet J Rare Dis 2016;11:159.|
|2||Syllaba L, Henner K. Contribution à l’indépendance de l’athétose double idiopatique et congénitale. Atteinte familiale, syndrome dystrophique, signe du réseau vasculaire conjonctival, intégrité psychique. Rev Neurol 1926;1:541-62.|
|3||Teive HA, Moro A, Moscovich M, Arruda WO, Munhoz RP, Raskin S, et al. Ataxia-telangiectasia––A historical review and a proposal for a new designation: ATM syndrome. J Neurol Sci 2015;355:3-6.|
|4||Boder E, Sedgwick RP. Ataxia-telangiectasia: A familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics 1958;21:526-54.|
|5||Taylor AM, Lam Z, Last JI, Byrd PJ. Ataxia telangiectasia: More variation at clinical and cellular levels. Clin Genet 2015;87:199-208.|
|6||Chessa L, Leuzzi V, Plebani A, Soresina A, Micheli R, D’Agnano D, et al. Intra-erythrocyte infusion of dexamethasone reduces neurological symptoms in ataxia telangiectasia patients: Results of a phase 2 trial. Orphanet J Rare Dis 2014;9:5.|
|7||Mahadevappa M, Kamble N, Santhosh Kumar DV, Yadav R, Netravathi M, Pal PK. A clinical profile of 100 patients with ataxia telangiectasia seen at a tertiary care center. Ann Mov Disord 2020;3:XX-XX.|