Spinocerebellar ataxia type 7: a neurodegenerative disorder with peripheral neuropathy.

BACKGROUND: Autosomal dominant spinocerebellar ataxias (SCA) are a group of inherited neurodegenerative disorders that typically show peripheral neuropathy. SCA7 is one of the rarest forms of SCA (<1/100,000 individuals). However, the disease shows a prevalence of ∼800/100,000 inhabitants in certain regions of Mexico. This low global prevalence may explain, at least in part, the isolated anecdotal and limited clinical data regarding peripheral neuropathy in SCA7 patients. AIM: To assess sensory and motor peripheral nerve action potentials in an SCA7 patients group and in healthy volunteers, and subsequently correlate the electrophysiological findings with clinical and genetic features. MATERIALS AND METHODS: We enrolled in our study, 13 symptomatic SCA7 patients with a confirmed molecular and clinical diagnosis, and 19 healthy volunteers as the control group. Nerve conduction studies were carried out using standard electromyography recording methods. The sensory and motor latency, amplitude and conduction velocity were recorded in both experimental groups and analyzed using the Student's t-test. RESULTS: SCA7 patients showed a significant prolongation of sensory nerve conduction latencies, as well as a decrease in sensory amplitudes. Decreases in motor amplitudes and peroneal conduction velocity were also observed. Finally, we found an association between CAG repeats and the severity of cerebellar and non-cerebellar symptoms with electrophysiological signs of demyelinization. DISCUSSION: Our results reveal the existence of a critical sensorimotor peripheral neuropathy in SCA7 patients. Moreover, we show that using sensitive electrophysiological tools to evaluate nerve conduction can improve the diagnosis and design of therapeutic options based on pharmacological and rehabilitative strategies. CONCLUSION: These findings demonstrate that SCA7 is a disease that globally affects the peripheral nervous system.

Altered Plasma Acylcarnitines and Amino Acids Profile in Spinocerebellar Ataxia Type 7.

Spinocerebellar ataxia type 7 (SCA7), a neurodegenerative disease characterized by cerebellar ataxia and retinal degeneration, is caused by an abnormal CAG repeat expansion in the ATXN7 gene coding region. The onset and severity of SCA7 are highly variable between patients, thus identification of sensitive biomarkers that accurately diagnose the disease and monitoring its progression are needed. With the aim of identified SCA7-specific metabolites with clinical relevance, we report for the first time, to the best of our knowledge, a metabolomics profiling of circulating acylcarnitines and amino acids in SCA7 patients. We identified 21 metabolites with altered levels in SCA7 patients and determined two different sets of metabolites with diagnostic power. The first signature of metabolites (Valine, Leucine, and Tyrosine) has the ability to discriminate between SCA7 patients and healthy controls, while the second one (Methionine, 3-hydroxytetradecanoyl-carnitine, and 3-hydroxyoctadecanoyl-carnitine) possess the capability to differentiate between early-onset and adult-onset patients, as shown by the multivariate model and ROC analyses. Furthermore, enrichment analyses of metabolic pathways suggest alterations in mitochondrial function, energy metabolism, and fatty acid beta-oxidation in SCA7 patients. In summary, circulating SCA7-specific metabolites identified in this study could serve as effective predictors of SCA7 progression in the clinics, as they are sampled in accessible biofluid and assessed by a relatively simple biochemical assay.