We performed an open-label prospective study: patients were evaluated clinically (ICARS scale, MRI and video-tape registration) at baseline and every 6 months during a period of 2 years after CoQ10 treatment (30 mg/Kg/day). Results: Patients with CoQ10 deficiency showed a statistically significant reduction of ICARS scores (Wilcoxon test: p=0.018) after 2 years of CoQ10 treatment as compared to baseline conditions. In patients without CoQ10 deficiency, no statistically significant differences were observed in total ICARS scores after therapy, although one patient from this group showed a remarkable clinical amelioration. Conclusions: Biochemical diagnosis of CoQ deficiency was a useful tool for the selection of patients who are good candidates for treatment, since all of them responded to therapy. However, the remarkable clinical response in one case without CoQ deficiency highlights the importance of treatment trials for identification of patients with CoQ-responsive ataxia. We report the case of a 32 years woman in whom an exercise test as been useful for the diagnosis of mitochondrial related myopathy and for the evaluation of the treatment efficiency. This patient presented abnormal fatigability who was later shown to be related with a multiple respiratory chain deficiency on muscle biopsy. An homoplasmic mutation (m.8322 T>C) in the tRNALysine gene has been found in this patient. Initial incremental exercise test demonstrated a pathological increase in peak serum lactate (9251 μmol.L-1), consistent with a predominant glycolytic anaerobic activity. Following the diagnosis confirmation (muscle biopsy, genetic) a treatment by L-Carnitine and Co-Q10 was initiated. A second exercise test was performed 4 months later (same protocol). It showed an increase in aerobic capacity, resulting in a greater maximal work rate exercise (96% vs 85% of predicted), higher oxygen uptake at peak (96% vs 89%) and at anaerobic threshold (71% vs 51%). In contrast, no change in peak serum lactate level was assessed. Larger studies are needed to confirm whether such treatment could lead to significant improvement of exercise performance. Mitochondrial diseases are a type of neurodegenerative disorders which are associated with mitochondrial respiratory chain deficiency in muscles and in a wide variety of tissues. They are caused by mutations in nuclear or mitochondrial genome, what leads to extremely heterogeneous clinical manifestation of these diseases. A dramatic example of such disorder is Leigh syndrome which mostly has onset at first years of life and frequently induced by mutations in SURF1 gene or T8993C/G substitution in mitochondrial DNA (mtDNA). However there's a wide range of patients with rare mutations in mtDNA. The etiology of a mutation and a proportion of mutant mtDNA in a cell define the severity of a disease. Thus, point mutations in mtDNA can lead to a clinical polymorphism, thereby complicating the finding of a causative mutation. We performed mtDNA sequence analysis of a group of patients (c. 50) with Leigh/Leighlike phenotype. A total 8 different substitutions were identified. Among these, 3 unknown mutations (C3945A, G8839C, T14441C) were found. Also 5 other mutations were identified: G3697A, T8362G, G8363A, T13094C, G13513A. On a base of our results we've developed a specific primers panel for MLPA analysis which allows us to hasten a search of mutations in mtDNA.