OP4 – 2557: Retrospective study of clinical presentation and diagnostic yield of cohort of children with suspected mitochondrial disease

Objective The diagnosis of mitochondrial disorders (MD) is complex and protracted, due to clinical and genetic heterogeneity, requiring collation of radiological, biochemical, histological and genetic investigations. Collaboration with mitochondrial expert neurologists, biochemists and geneticists in the UK helps to achieve the best diagnostic rates of MD. The aim of the study was to determine the clinical characteristics of children with suspected and confirmed MD, review the yield of investigations and recommend best practice. Methods All children with suspected MD seen August 2008 to July 2014, within Cambridge paediatric neuroscience, had expert review of their presentation and investigations at an annual multidisciplinary mitochondrial group meeting by paediatric neurology, biochemistry, genetics, neuropathology, mitochondrial genetics, academic mitochondrial specialists within our tertiary centre, London, Oxford and Newcastle national mitochondrial centres. Results 28 children were identified, age range: 14 days–13 years (7 had died at 14 days–4 years), who were predominantly of Caucasian origin. The most common clinical presentation was developmental delay (71%) and refractory seizures (64%), MRI was suggestive of MD in 17%. MD was genetically confirmed in 20% and on respiratory chain abnormality (RCE) in 7%. RCE analysis proved beneficial in detecting abnormalities when initial histology was normal or indicative of alternative pathology. 25% of children have been recruited for next generation exome sequencing. Conclusion Diagnostic delay in MD is common due to the complex nature of investigations. The low rate of genetic diagnosis in our cohort is similar to other reported case series. Next generation sequencing and biomarkers such as FGF21 are promising diagnostic tools that may improve diagnostic accuracy. Expert review of the cases by the designated mitochondrial disease centres in the UK improves diagnostic accuracy.