Diagnostic Value of Next Generation Sequencing Ataxia Panel as a Part of Multistep Investigation Approach in Sporadic and Autosomal Recessive Cerebellar Ataxias in Russia (P1.8-013)

April 09, 2019; 92 (15 Supplement) MAY 5, 2019
 
Yury Seliverstov, Evgenii Nuzhnyi, Sergey Klyushnikov, Natalia Abramycheva, Anna Vetchinova, Sergei Illarioshkin
First published April 9, 2019,
 

Objective: To investigate the spectrum of sporadic and autosomal recessive cerebellar ataxias (SARCAs) in patients under 50 years of age in the Russian population using a multistep diagnostic approach with a next generation sequencing ataxia panel (NGSAP).

Background: Due to a high variability in clinical presentation, SARCAs often represent a diagnostic challenge for a clinician.

Design/Methods: During the period of September 2016–July 2018, we analyzed 52 patients under 50 years of age who were referred to our centre with SARCAs. First step implied thorough exclusion (including brain MRI) of acquired cerebellar ataxia and multiple system atrophy (MSA). Second step included tests for SCA types 1, 2, 3, 6, 8, and 17 along with Friedreich’s ataxia (FA). At the third step, certain laboratory tests along with biochemical screening for NP-C, Gaucher’s disease, and GM2-gangliosidoses were done. Third step also included ophthalmic exam, electromyography, and abdominal ultrasound. The final step implied a NGSAP with further interpretation based on (but not limited to) data obtained at the third step.

Results: At the first step, 6 patients were found to have acquired cerebellar ataxia and 2 patients was diagnosed with MSA. At the second step, 3 patients turned to be positive for SCA types 1, 2, and 17 along with 9 patients positive for FA. After the third step, 32 patients underwent NGSAP (136 genes) based on Illumina MiSeq platform. NGSAP allowed to diagnose ataxia-telangiectasia (n=5), ataxia with oculomotor apraxia type 1 (n=1) and type 2 (n=1), SANDO syndrome (n=2), Krabbe disease (n=1), ARCA3 (n=1), SCAR16 (n=1), and NBIA2A (n=1). In 19 patients NGSAP was negative for clinically significant mutations.

Conclusions: Non-hereditary cerebellar ataxias represented 15.4% of SARCAs. FA was the most frequent (17.3%) hereditary SARCA. Being a part of the multistep approach, NGSAP provides a positive diagnostic yield in 40.6% of undiagnosed patients with SARCAs in Russian population.

Disclosure: Dr. Seliverstov has nothing to disclose. Dr. Nuzhnyi has nothing to disclose. Dr. Klyushnikov has nothing to disclose. Dr. Abramycheva has nothing to disclose. Dr. Vetchinova has nothing to disclose. Dr. Illarioshkin has nothing to disclose.