G259 Mitochondrial DNA disease in children

Abstract

Mitochondrial DNA disease in childhood is notoriously difficult to diagnose clinically due to the wide spectrum of clinical presentations, phenotypic heterogeneity and non-specific symptoms. Diagnosis can therefore be difficult which may result in delayed and/or unnecessary investigations. Aims To identify common disease features in children with mtDNA disease and to compare disease features and clinical progression in children belonging to the same family pedigree. Methods Retrospective review of medical records, prospective clinical assessments and NPMDS scores were utilized to obtain clinical data. Assessment took place at 3–12 monthly intervals by a clinician with expertise in mitochondrial disease. Inclusion criteria for this study included live males and females aged under 21 years on 01/01/2010 harbouring a known pathogenic mtDNA mutation, attending the NHS Highly Specialised Services for Rare Mitochondrial Diseases in Newcastle-upon-Tyne and/or consented to the MRC MitoCohort Study UK. Results 53 children were studied (male:female ratio=1:1.3). There were 32 families within this study, with the child studied being the index case in 18 (34%) cases. In those families harbouring the m.3243A>G mtDNA mutation, where two or more children were affected the male relative had more significant disease burden than the female relative, regardless of heteroplasmy level. The most commonly affected system at presentation was the central nervous system, followed by the endocrine system and the gastro-intestinal system. The predominant clinical symptoms at presentation were sensori-neural hearing loss and developmental regression and/or developmental delay. There was a delay of over 3 years between age at symptom onset and age at diagnosis, excluding those who were asymptomatic. 7 children died due to their mtDNA disease(male:female=6:1). Time from symptom onset to death ranged from 3 years to 23 years. Conclusion This is the largest study of children with mtDNA disease to date and has identified common disease features, the spectrum of presentation as well as disease progression. Children with symptoms involving 3 or more body systems and no unifying diagnosis warrant further investigation. Children with a positive family history of mtDNA disease should also be referred for assessment, as may benefit from genetic counselling, but should also be referred for cardiac and audiological screening