[Diagnostic algorithm for autosomal recessive ataxia]. / Algoritm diagnostiki autosomno-retsessivnykh ataksii.

AIM: To develop a complex algorithm for autosomal recessive ataxia (ARA) diagnosis applicable for Russian patients with degenerative ataxias. MATERIAL AND METHODS: 48 patients with of presumably degenerative ataxias were examined. Clinical evaluation was performed with the use of the SARA and ICARS scales (for ataxia) and MoCA (cognitive functions), and a set of laboratory tests was carried out, including electromyography, brain MRI, and DNA analysis of mutations responsible for Friedreich's disease and spinocerebellar ataxias (SCAs) types 1, 2, 3, 6 and 17. 28 patients underwent mutation screening using a multigenic MPS panel. RESULTS: 8 patients (16.7%) with non-hereditary causes of ataxia were identified: cerebellar alcoholic degeneration (n = 6) and multiple system atrophy of cerebellar type (n = 2); 3 patients (6.3%) with genetic ataxias were identified using routine DNA tests, such as with SCA type 1, 2 and 17, and 9 (18.8%) patients with Friedreich's disease. The MPS panel enabled molecular diagnosis of ARA in 8 patients (28.6%): ataxia-telangiectasia (n = 2), SANDO syndrome (n = 2), ataxia with oculomotor apraxia type 2 (n = 1), SCAR10 (n = 1), SCAR16 (n = 1), and atypical form of neuroaxonal dystrophy (n = 1). The diagnosis was not established in 20 patients. CONCLUSION: We have proposed an appropriate algorithm for degenerative ataxia diagnosis which is recommended to be used when examining patients with sporadic and autosomal recessive cases of the disorders with dyscoordination of movements.

Molecular Pathogenesis in Huntington's Disease.

Huntington's disease (HD) is a severe autosomal dominant neurodegenerative disorder characterized by a combination of motor, cognitive, and psychiatric symptoms, atrophy of the basal ganglia and the cerebral cortex, and inevitably progressive course resulting in death 5-20 years after manifestation of its symptoms. HD is caused by expansion of CAG repeats in the HTT gene, which leads to pathological elongation of the polyglutamine tract within the respective protein - huntingtin. In this review, we present a modern view on molecular biology of HD as a representative of the group of polyglutamine diseases, with an emphasis on conformational changes of mutant huntingtin, disturbances in its cellular processing, and proteolytic stress in degenerating neurons. Main pathogenetic mechanisms of neurodegeneration in HD are discussed in detail, such as systemic failure of transcription, mitochondrial dysfunction and suppression of energy metabolism, abnormalities of cytoskeleton and axonal transport, microglial inflammation, decrease in synthesis of brain-derived neurotrophic factor, etc.