Background Mitochondrial disease are multi-system disorders affecting virtually any organ and cause significant morbidity. The prevalence of mitochondrial DNA (mtDNA) disease is estimated at 1 in 5000, but epidemiological studies suggest that at least 1 in 200 healthy humans harbour a pathogenic mtDNA mutation. The m.3243A>G mutation in the MTTL1 gene is one of the commonest mtDNA mutations and can cause several clinical phenotypes including Mitochondrial Encephalopathy, Lactic Acidosis, Stroke-like episodes (MELAS), Chronic Progressive External Ophthalmoplegia (CPEO) and Maternally Inherited Deafness and Diabetes (MIDD). Additional features associated with these syndromes include migraine, bowel dysmotility, and short stature.

Aims To review the phenotypic spectrum of the m.3243A>G mtDNA mutation in children and young adults.

Methods Patients were identified from the MRC Mitochondrial Disease Patient Cohort Study UK, and the NHS Specialist Service for Mitochondrial Diseases in Newcastle upon Tyne. Retrospective review of medical notes and clinical investigations was performed.

Results Data was collected on 21 children and young adults (7 male, 14 female). Seven (33%) were the index case (4 male, 3 female) with the mutation identified in the mother in six of the index cases reflecting maternal transmission. Two patients had a clinical phenotype consistent with MELAS (10%), no patients had a classical CPEO or MIDD phenotype. Three patients exhibited a Leigh's phenotype (14%). 14 patients (67%) had three or more clinical systems involved. 16 patients (76%) were below the 25th centile for height and weight. 17 patients (81%) experience gut dysmotility or constipation, 12 patients (57%) exhibited signs of developmental delay, 9 patients (43%) had hearing impairment, 5 patients (24%) had cardiac manifestations of mtDNA disease, 3 patients (14%) had renal impairment.

Conclusions The spectrum of clinical features exhibited by children with the m.3243A>G mutation is broad, but few children fulfil clinical criteria for the classical syndromes associated with this mutation. Children presenting with multisystem disease, particularly in the presence of a maternal family history of short stature, deafness, cardiac disease, gut dysmotility or unexplained death should be investigated for possible mtDNA disease.