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Introduction The mitochondrial DNA m.3243A > G mutation is the most prevalent mutation causing mitochondrial disease in adult patients. Aside from some case reports, there are no studies on obstetric complications in a cohort of m.3243A > G carriers. We aimed to identify the prevalence of obstetric complications in a cohort of women carrying the m.3243A > G mutation. Methods All female carriers of the m.3243A > G mutation known from our previous national inventory were sent a questionnaire regarding their obstetric history. Data were compared to national references. Data from the national inventory, including NMDAS (disease severity) scores and heteroplasmy levels in urinary epithelial cells (UEC) were used to stratify women. Results Sixty women participated, the mean age was 47 years (range 20–70), mean NMDAS was 14.6 (range 0–46), and mean heteroplasmy percentage in UEC was 19.9% (range 5–85%). Ninety-eight pregnancies in 46 women were reported. Twenty-three (25.3%) had a premature delivery and five of them (5.5%) had a gestation of ≤ 32 weeks and eleven of the women (12%) suffered from preeclampsia. No different heteroplasmy level was found in the women with preeclampsia. Nine pregnancies (11%) were complicated by gestational diabetes. Discussion Obstetric complications occur frequently in carriers of the m.3243A > G mutation. Proper guidance during pregnancies and early detection of possible obstetric complications are needed. As techniques to prevent transmission of mitochondrial mutations are studied it is important to know the possible complications patients may experience from the ensuing pregnancy. [ABSTRACT FROM AUTHOR]

Background: The mitochondrial DNA m.3243A>G mutation is one the most prevalent mutation causing mitochondrial disease in adult patients. Several cohort studies have used heteroplasmy levels in urinary epithelial cells (UEC) to correlate the genotype of the patients to the clinical severity. However, the interpretation of these data is hampered by a lack of knowledge on the intra‐patient variability of the heteroplasmy levels. The goal of this study was to determine the day‐to‐day variation of the heteroplasmy levels in UEC. Methods: Fifteen carriers of the m.3243A>G mutation collected five urine samples in a 14‐day window. Heteroplasmy levels of the m.3243A>G mutation were determined in these samples. Data from the national cohort study, including Newcastle Mitochondrial Disease Adult Scale scores and clinical diagnosis, were used. Results: In the samples of six patients, heteroplasmy levels were within a 5% margin. In the samples collected from five patients, the margin was >20%. Conclusion: Heteroplasmy levels of UEC in carriers of the m.3243A>G mutation have a significant day‐to‐day variation. The interpretation of a correlation between heteroplasmy levels in urine and disease severity is therefore not reliable. Therefore, heteroplasmy levels in UEC should not be used as a prognostic biomarker in these patients. In this study, we showed that the measurement of heteroplasmy in urinary epithelial cells has a substantial intra‐patient variability and is therefore unfit to be used as a prognostic biomarker in patients carrying the m.3243A>G mutation. This should be taken into account in the evaluation of relevant biomarkers for carriers of the m.3243A>G mutation. [ABSTRACT FROM AUTHOR]

KH176 is a potent intracellular reduction-oxidation-modulating compound developed to treat mitochondrial disease. We studied tolerability, safety, pharmacokinetics, pharmacodynamics, and efficacy of twice daily oral 100 mg KH176 for 28 days in a double-blind, randomized, placebo-controlled, two-way crossover phase IIA study in 18 adult m.3243A>G patients without cardiovascular involvement. Efficacy parameters included clinical and functional outcome measures and biomarkers. The trial was registered within ClinicalTrials.gov (NCT02909400), the European Clinical Trials Database (2016-001696-79), and ISRCTN (43372293) (The KHENERGY study). Twice daily oral 100 mg KH176 was well tolerated and appeared safe. No serious treatment-emergent adverse events were reported. No significant improvements in gait parameters or other outcome measures were obtained, except for a positive effect on alertness and mood, although a coincidence due to multiplicity cannot be ignored. The results of the study provide first data on safety and efficacy of KH176 in patients with mitochondrial disease and will be instrumental in designing future clinical trials., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)