Urogenital symptoms in mitochondrial disease: overlooked and undertreated.

BACKGROUND AND PURPOSE: Bowel symptoms are well documented in mitochondrial disease. However, data concerning other pelvic organs is limited. A large case-control study has therefore been undertaken to determine the presence of lower urinary tract symptoms (LUTS) and sexual dysfunction in adults with genetically confirmed mitochondrial disease. METHODS: Adults with genetically confirmed mitochondrial disease and control subjects were recruited from a specialist mitochondrial clinic. The presence and severity of LUTS and their impact on quality of life, in addition to sexual dysfunction and bowel symptoms, were captured using four validated questionnaires. Subgroup analysis was undertaken in patients harbouring the m.3243A>G MT-TL1 mitochondrial DNA mutation. A subset of patients underwent urodynamic studies to further characterize their LUTS. RESULTS: Data from 58 patients and 19 controls (gender and age matched) were collected. Adults with mitochondrial disease had significantly more overactive bladder (81.5% vs. 56.3%, P = 0.039) and low stream (34.5% vs. 5.3%, P = 0.013) urinary symptoms than controls. Urodynamic studies in 10 patients confirmed that bladder storage symptoms predominate. Despite high rates of LUTS, none of the patient group was receiving treatment. Female patients and those harbouring the m.3243A>G MT-TL1 mutation experienced significantly more sexual dysfunction than controls (53.1% vs. 11.1%, P = 0.026, and 66.7% vs. 26.3%, P = 0.011, respectively). CONCLUSIONS: Lower urinary tract symptoms are common but undertreated in adult mitochondrial disease, and female patients and those harbouring the m.3243A>G MT-TL1 mutation experience sexual dysfunction. Given their impact on quality of life, screening for and treating LUTS and sexual dysfunction in adults with mitochondrial disease are strongly recommended.

Single deletions in mitochondrial DNA--molecular mechanisms and disease phenotypes in clinical practice.

Over 20 years ago single clonal deletions were the first mitochondrial DNA (mtDNA) genetic defects described in association with human disease. Since then very large numbers of children and adults harbouring such deletions have been described and it is clear they are an important cause of human mitochondrial disease. However, there still remain many important challenges in relation to our understanding of mechanisms leading to deletion formation and propagation and in relation to the factors determining the complex and varying relationship between genotype and clinical phenotype. Although multidisciplinary team care is essential and can improve quality of life and outcomes for patients, a definitive molecular treatment for single mtDNA deletions remains an important translational research goal. Patients with mtDNA deletions exhibit a very wide range of different clinical phenotypes with marked variation in age at onset and disease severity. Single mtDNA deletions may enter into the differential diagnosis of many different paediatric and adult presentations across a wide range of medical specialties, although neurological presentations are amongst the most common. In this review, we examine the molecular mechanisms underpinning mtDNA replication and we consider the hypotheses proposed to explain the formation and propagation of single large-scale mtDNA deletions. We also describe the range of clinical features associated with single mtDNA deletions, outline a molecular diagnostic approach and discuss current management including the role of aerobic and resistance exercise training programmes.