Mitochondrial DNA testing increases the diagnostic efficacy of mitochondrial disorders by 8.3%

Background: Mitochondrial disorders can be caused by defects in nuclear or mitochondrial DNA (mtDNA). mtDNA testing in Tartu University Hospital (TUH), the only tertiary care unit in Estonia for diagnosing patients with genetic disorders, started in 2015. First, mtDNA sequencing analysis was implemented. In 2017, MLPA analysis was added, which detects deletions, duplications and six main pathogenic variants in mtDNA. This work aims to summarise the data from the last eight years.

Materials and methods: Data on mtDNA analyses and findings from 2015-2022 were obtained from the TUH molecular diagnostics laboratory and analysed retrospectively. Patients ranged from fetal to 83 years of age

Results: In total, 336 patients were analysed, and 459 analyses were performed. The disease-causing variant was found in 28 patients (8.3%). Of these variants, 26 (93%) were point mutations and two (7%) were deletions. A total of 11 different variants were found. Seven patients (25%) had a primary finding from mtDNA sequencing analysis and 21 patients (75%) from MLPA analysis. On average, 1.4 analyses were performed, and 1.2 tissues were examined per patient. Only one tissue was investigated in 84% of individuals, and in 16% of patients, two or more tissues were tested. The most commonly tested tissue was blood, followed by urine. Three patients had a negative result on blood analysis, but the disease-causing variant was found in another tissue. The most common variant identified was m.3243A>G in MT-TL1.

Discussion/Conclusion: Mitochondrial disease was diagnosed in 8.3% of those studied, but only one tissue was examined in 84% of cases. The most common variant identified is also the most prevalent mtDNA pathogenic variant described in the literature. The number of analyses and tissues tested per person is low. If a mitochondrial disease is suspected, a negative result should be followed up with further tests and tissues other than blood should be examined.

Funding: PRG471, PSG774.