Phenotypes and Genotypes of Mitochondrial Disease- Findings from A National Mitochondrial Disease Cohort (P2.061)

Objective: To better understand the demographic distribution of mitochondrial disease, phenotypic and genotypic variability and progression associated with mitochondrial disease. Background: The phenotypic and genotypic heterogeneity in mitochondrial disease often poses a considerable diagnostic challenge to clinicians and scientists. To date, there are few effective treatments and no known cure for mitochondrial disorders hence supportive care with multi-disciplinary input remains a fundamental element in daily clinical practice. However, the lack of natural history makes prognostication, long-term management, genetic counselling and discussion of reproductive options extremely difficult. Methods: The MRC Mitochondrial Disease Patient Cohort Study (UK) was developed in 2009. Patients with biochemical and/or genetic evidence of mitochondrial disease are recruited from three principal mitochondrial disease centres (Newcastle, London and Oxford) with additional 9 secondary centres. Data collated both retrospectively and prospectively include clinical phenotype, family pedigree, molecular genetics, muscle biopsy findings, blood tests, neurophysiological evaluation, brain and cardiac imaging investigations and Newcastle Mitochondrial Disease Adult Scale (NMDAS) scores in a systematic fashion. NMDAS and its paediatric equivalence are used to examine individual disease burden and progression. Results: There are 1165 patients (85[percnt] are adults) registered on the cohort. Sixty-five percent of patients have primary mitochondrial DNA mutations, 23[percnt] have mutations in nuclear genes and 12[percnt] have biochemical evidence of mitochondrial disease but genetically undetermined. The common neurological features (based on NMDAS, n=452) are myopathy (64[percnt]), chronic progressive external ophthalmoplegia (40[percnt]), cerebellar ataxia (39[percnt]), cognitive impairment (33[percnt]), dysphagia (21[percnt]), epilepsy (19[percnt]) and stroke-like episode (9[percnt]). Other systemic involvements are gastrointestinal (44[percnt]), endocrine/diabetes (22[percnt]) and cardiac (20[percnt]). Conclusion: This national cohort offers a unique opportunity to deep phenotype a large group of mitochondrial disease patients, bridge the gap in our understanding of disease progression, develop clinical guideline on patient care and facilitate patient recruitment for any future trials. Disclosure: Dr. Ng has nothing to disclose. Dr. Gorman has nothing to disclose. Dr. Nesbitt has nothing to disclose. Dr. Pitceathly has nothing to disclose. Dr. Grady has nothing to disclose. Dr. Schaefer has nothing to disclose. Dr. Bright has nothing to disclose. Dr. Feeney has nothing to disclose. Dr. Rahman has nothing to disclose. Dr. Poulton has nothing to disclose. Dr. Taylor has nothing to disclose. Dr. Hanna has received personal compensation for activities with Bristol-Myers Squibb as an employee. Dr. Turnbull has nothing to disclose. Dr. McFarland has nothing to disclose.