Humans ; Mitochondrial Diseases/therapy* ; DNA, Mitochondrial/genetics*

The mammalian mitochondrial ATP synthase, also as known as mitochondrial respiratory chain complex V, is a large protein complex located in the mitochondrial inner membrane, where it catalyzes ATP synthesis from ADP, Pi, and Mg2+ at the expense of an electrochemical gradient of protons generated by the electron transport chain. Complex V is composed of 2 functional domains F0 and F1. The clinical features of patients are significantly heterogeneous depending on the involved organs. Most patients with complex V deficiency had clinical onset in the neonatal period with severe brain damage or multi-organ failure resulting in a high mortality. Neuromuscular disorders, cardiomyopathy, lactic acidosis and 3-methylglutaconic aciduria are common findings. Complex V consists of 16 subunits encoded by both mitochondrial DNA and nuclear DNA. On MT-ATP6, MT-ATP8, ATPAF2, TMEM70 and ATP5E gene of mitochondrial DNA, many mutations associated with Complex V deficiency have been identified. Here, the pathology, clinical features, diagnosis, treatment and molecular genetics of Complex V deficiency were summarized.
Mitochondrial Diseases ; complications ; etiology ; therapy ; Mitochondrial Proton-Translocating ATPases ; chemistry ; deficiency ; genetics ; physiology ; Prognosis

Nuclease-based gene editing technologies have opened up opportunities for correcting human genetic diseases. For the first time, scientists achieved targeted gene editing of mitochondrial DNA in mouse oocytes fused with patient cells. This fascinating progression may encourage the development of novel therapy for human maternally inherent mitochondrial diseases.
Animals ; DNA, Mitochondrial ; genetics ; Embryo, Mammalian ; metabolism ; Genome ; Germ Cells ; metabolism ; Humans ; Mitochondrial Diseases ; genetics ; therapy ; RNA Editing ; genetics

Diffuse Cerebral Sclerosis of Schilder ; diagnosis ; therapy ; Epilepsy ; etiology ; therapy ; Humans ; Mitochondrial Diseases ; complications

The aim of this study was to investigate the clinical features and DGUOK gene mutations of an infant with mitochondrial DNA depletion syndrome (MDS). The patient (more than 7 months old) manifested as hepatosplenomegaly, abnormal liver function, nystagmus and psychomotor retardation. Genetic DNA was extracted from peripheral blood samples of the patient and her parents. Targeted Exome Sequencing was performed to explore the genetic causes. Sanger sequencing was carried out to confirm the detected mutations. The sequencing results showed that the patient was a compound heterozygote for c.679G>A and c.817delT in the DGUOK gene. The former was a reportedly pathogenic missense mutation of maternal origin, while the latter, a frameshift mutation from the father, has not been described yet. The findings in this study expand the mutation spectrum of DGUOK gene, and provide molecular evidence for the etiologic diagnosis of the patient as well as for the genetic counseling and prenatal diagnosis in the family.
Female ; Humans ; Infant ; Mitochondrial Diseases ; genetics ; therapy ; Mutation ; Phosphotransferases (Alcohol Group Acceptor) ; chemistry ; genetics

This article reviews the structure and function of mitochondrial respiratory chain complex Ⅱ, and the clinical features, diagnosis, treatment and genetic analysis of mitochondrial respiratory chain complex Ⅱ deficiency. Mitochondrial complex Ⅱ, known as succinate dehydrogenase, is a part of the mitochondrial respiratory chain. It plays an important role in cellular oxidative phosphorylation. It is associated with oxidative stress and is a sensitive target for toxic substances and abnormal metabolin in cells. Clinical manifestations of respiratory chain complex Ⅱ deficiency are characterized by a wide variety of abnormalities. Progressive neuromuscular dysfunction is the most common syndrome. Cardiomyopathy, episodic vomit and hemolytic uremic syndrome are also encountered in a few cases. A precise diagnosis is dependent on enzyme activities assay of respiratory chain complexes and genetic analysis. Complex Ⅱ activities decreased in affected tissues. Pathogenic mutations in SDHA gene and SDHAF1 gene encoding assembly factor have been found so far. Clinical treatment aims at improving the mitochondrial function.
Animals ; Electron Transport Complex II ; chemistry ; deficiency ; physiology ; Female ; Humans ; Male ; Mitochondrial Diseases ; diagnosis ; genetics ; therapy

The human mitochondrial genome consists of approximate 1500 genes, among which 37 are encoded by the mitochondrial DNA (mtDNA) and the remainder encoded in the nuclear DNA (nDNA). The mitochondria produces large amount of the cellular reactive oxygen species (ROS). ROS induces the mutations of mtDNA and mtDNA, which are associated with a wide range of age-related diseases including neurodegenerative diseases, cardiomyopathy, diabetes and various cancers.
Aging ; DNA, Mitochondrial ; genetics ; Genetic Therapy ; Humans ; Mitochondria ; genetics ; metabolism ; Mutation ; Neurodegenerative Diseases ; genetics ; therapy ; Reactive Oxygen Species ; metabolism

Apoptosis ; Cell Nucleus ; metabolism ; Clinical Trials as Topic ; Cytoplasm ; metabolism ; DNA, Mitochondrial ; metabolism ; Glucocorticoids ; therapeutic use ; Humans ; MELAS Syndrome ; drug therapy ; Mitochondria ; metabolism ; Mitochondrial Diseases ; drug therapy ; Muscular Diseases ; drug therapy

The velopharynx is a tridimensional muscular valve located between the oral and nasal cavities, consisting of the lateral and posterior pharyngeal walls and the soft palate, and controls the passage of air. Velopharyngeal insufficiency may take place when the velopharyngeal valve is unable to perform its own closing, due to a lack of tissue or lack of proper movement. Treatment options include surgical correction, prosthetic rehabilitation, and speech therapy; though optimal results often require a multidisciplinary approach for the restoration of both anatomical and physiological defect. We report a case of 56 year old male patient presenting with hypernasal speech pattern and velopharyngeal insufficiency secondary to cleft palate which had been surgically corrected 18 years ago. The patient was treated with a combination of speech therapy and palatal lift prosthesis employing interim prostheses in various phases before the insertion of definitive appliance. This phase-wise treatment plan helped to improve patient's compliance and final outcome.
Cleft Palate ; Compliance ; Humans ; Hypogonadism ; Male ; Mitochondrial Diseases ; Nasal Cavity ; Ophthalmoplegia ; Palate, Soft ; Prostheses and Implants ; Speech Therapy ; Velopharyngeal Insufficiency

OBJECTIVE: The authors present their experiences with stereotactic multiplanar reformatted (MPR) computed tomography (CT)-guided catheter placement for thrombolysis of spontaneous intracerebral hematoma (sICH) and their clinical results. METHODS: In 23 patients with sICH, MPR CT-guided catheter placement was used to select the trajectory and target point of hematoma drainage. This group was comprised of 11 men and 12 women, and the mean age was 57.5 years (range, 31-79 years). The patients' initial Glasgow Coma Scale scores ranged from 7 to 15 with a median of 11. The volume of the hematoma ranged from 24 mL to 86 mL (mean 44.5 mL). A trajectory along the main axis of the hematoma was considered to be optimal for thrombolytic therapy. The trajectory was calculated from the point of entry through the target point of the hematoma using reformatted images. RESULTS: The hematoma catheter was left in place for a median duration of 48.9 hours (range 34 to 62 hours). In an average of two days, the average residual hematoma volume was 6.2 mL (range 1.4 mL to 10.2 mL) and was reduced by an average of 84.7% (range 71.6% to 96.3%). The residual hematoma at postoperative seven days was less than 5 mL in all patients. There was no treatment-related death during hospitalization. CONCLUSION: The present study indicates that stereotactic MPR CT-guided catheter placement for thrombolysis is an accurate and safe procedure. We suggest that this procedure for stereotactic removal of sICH should be considered for the optimization of the trajectory selection in the future.
Axis, Cervical Vertebra ; Catheters ; Drainage ; Female ; Glasgow Coma Scale ; Hematoma ; Hospitalization ; Humans ; Hypogonadism ; Male ; Mitochondrial Diseases ; Ophthalmoplegia ; Thrombolytic Therapy