ONLINE MUTATION REPORT Compensatory amplification of mtDNA in a patient with a novel deletion/duplication and high mutant load

T he clinical manifestations of patients with mitochondrial DNA (mtDNA) deletions are quite variable. Kearns-Sayre syndrome (KSS; OMIM #530000), the most commonly recognised phenotype, is characterised by the diagnostic triad of progressive external ophthalmoplegia (PEO, OMIM #555000), onset before 20 years of age, pigmentary retinopathy, and one or more of the following: cerebellar ataxia, cardiac conduction defect, and/or elevated protein concentration of greater than 1 g/L in cerebrospinal fluid. Other phenotypes associated with mtDNA deletions include chronic progressive external ophthalmoplegia, Pearson marrowpancreas syndrome, Addison disease, diabetes mellitus, cyclic vomiting, deafness, optic atrophy, and renal tubulopathy. KSS typically occurs in adult patients, and the deleted mutant mtDNA is usually not present in blood. On the other hand, the clinical presentation of mtDNA deletion syndromes in infants and young children is variable and does not necessarily feature the classic symptoms seen in KSS. In severe cases with multisystemic involvement, a high percentage of deleted mutant mtDNA is present in all tissues examined. We describe a 41 year old woman who presented with atypical KSS at the age of 30 years. A novel mtDNA deletion was detected in both muscle and blood specimens of this patient, despite the finding of respiratory chain enzymes in the normal range in muscle samples.