Sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO syndrome): characteristics of a series of clinical observations in Russia

Abstract

Introduction. Mitochondrial ataxias are an extremely heterogeneous group of diseases, which include the SANDO (an acronym stands for sensory ataxic neuropathy, dysarthria and ophthalmoparesis) syndrome. SANDO syndrome is one of the characteristic phenotypes associated with mutations in the POLG gene. Study objective. To analyse the clinical picture and the results of clinical and laboratory tests in a Russian case series of genetically confirmed SANDO syndrome. Materials and methods. Nine patients (4 men and 5 women aged 33.4±11.3 years) with SANDO syndrome and identified mutations in the POLG gene were examined. A clinical evaluation using the SARA and ICARS (for ataxia) and MoCA (cognitive function) scales, laboratory study of liver function, electrocardiography, stimulation electromyography and brain MRI were performed; 6 patients underwent electroencephalography. MLPA analysis and the original multigene NGS panel were used for genetic screening. Results. The average age of disease onset was 27.7±8.2 years, with significant variability (from 14 to 49 years). The disease was characterized by a rather typical clinical picture, which included sensory ataxia, polyneuropathy, dysarthria and external ophthalmoparesis in all patients; the median score was 13.5/40 [11; 25] points on the SARA scale, 39.5/100 [33; 63] points on the ICARS scale, and 22 [20; 25] points on the MoCA scale. Two patients showed signs of frontal lobe dysfunction. In most patients, MRI revealed changes in the white matter of the cerebellar hemispheres, brainstem, thalamus and semioval centres, but no pathology was detected on MRI in 3 patients. The p.W748S mutation in the POLG gene made up 83% of the mutant alleles, while the p.L931R and p.L311P pathogenic mutations found in 2 patients are new variants and have not been described in international databases. Conclusion. Our findings suggest that the true frequency of SANDO syndrome in the population may be higher than previously thought. Therefore, a suspicion of this disease should be maintained even in the absence of characteristic changes on neuroimaging. For the timely detection of SANDO syndrome, we propose an appropriate diagnostic algorithm, which should be followed when examining patients with ataxia.