1/8. Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene.The Mohr-Tranebjaerg syndrome (MIM 304700) and the Jensen syndrome (MIM 311150) were previously reported as separate X-linked recessive deafness syndromes associated with progressive visual deterioration, dystonia, dementia, and psychiatric abnormalities. In the most extensively studied Norwegian family, the Mohr-Tranebjaerg syndrome was reported to be caused by a one-basepair deletion (151delT) in the deafness/dystonia peptide (DDP) gene at Xq22. This gene has been renamed TIMM8a. We identified a stop mutation (E24X) in the TIMM8a gene segregating with the disease in the original Danish family with the Jensen syndrome, which confirms that the two disorders are allelic conditions. We also report abnormal VEP examinations and neuropathological abnormalities in affected males from the two unrelated families with different mutations. The findings included neuronal cell loss in the optic nerve, retina, striate cortex, basal ganglia, and dorsal roots of the spinal cord. The demonstration of mitochondrial abnormalities in skeletal muscle biopsies in some patients is compatible with the suggestion from recent research that the TIMM8a protein is the human counterpart of an intermembrane mitochondrial transport protein, Tim8p, recently characterized in yeast. The clinical and neuropathological abnormalities associated with mutations in the TIMM8a gene support that this X-linked deafness-dystonia-optic neuropathy syndrome is an example of progressive neurodegeneration due to mutations in a nuclear gene necessary for some, yet unknown mitochondrial transport function. We recommend sequencing the TIMM8a gene, thorough ophthalmological examination, and measuring visual evoked potentials in clinically suspected male patients with either progressive hearing impairment, dystonia, or visual disability in order to establish an early diagnosis and provide appropriate genetic counselling.- - - - - - - - - - ranking = 1keywords = hearing (Clic here for more details about this article) |
2/8. Renal complications in a patient with A-to-G mutation of mitochondrial dna at the 3243 position of leucine tRNA.A 27-year-old woman with short stature, sensorineural deafness, and renal dysfunction was hospitalized for evaluation. The serum lactate and pyruvate concentrations were elevated. The analysis of her mitochondrial dna revealed an A-to-G mutation of the tRNA(Leu (UUR)) gene at the 3243 position. Renal biopsy revealed many sclerotic glomeruli, advanced tubulointerstitial changes, and numerous swollen mitochondria of the tubular cells. It was concluded that the patient's mitochondrial gene mutation was etiologically related to her nephropathy. The clinicopathologic features of this patient, as contrasted to the previous reports, suggested that renal involvement due to this mitochondrial gene mutation can be heterogeneous.- - - - - - - - - - ranking = 2.7273041595952keywords = sensorineural (Clic here for more details about this article) |
3/8. External ophthalmoplegia with severe progressive multiorgan involvement associated with the mtDNA A3243G mutation.BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) may be related to primary nuclear dna or mitochondrial (mt)dna mutations. The A3243G mtDNA point mutation most frequently causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, but also has been associated with other phenotypes including CPEO, migraine, seizure, diabetes, and sensorineural hearing loss. CASE DESCRIPTION: We report a 38-year-old white man with seizures and progressive difficulties of infantile origin including CPEO, sensorineural hearing loss, cataracts, migraines, multiple endocrinopathy, myopathy, and cardiomyopathy. Moderate hearing loss in association with CPEO, diabetes mellitus, or migraines were noted in the proband's maternal grandmother, great aunt, mother, and three sisters, suggesting either an autosomal dominant or maternal inheritance. Detailed histological and biochemical analysis of the proband's biopsied muscle specimen revealed severe abnormalities compatible with a mitochondrial disease. MtDNA analysis excluded large-scale deletions, but revealed a heteroplasmic A to G transition at nt3243 in 56.4% and 27.4% of molecules in muscle and white blood cells, respectively. CONCLUSION: We discuss possible causes of this intrafamilial heterogeneity of phenotypes associated with the A3243G mtDNA mutation.- - - - - - - - - - ranking = 29.919066136394keywords = sensorineural hearing loss, sensorineural hearing, sensorineural, hearing loss, hearing (Clic here for more details about this article) |
4/8. Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency.CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I III and II III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.- - - - - - - - - - ranking = 13.32769838055keywords = sensorineural hearing loss, sensorineural hearing, sensorineural, hearing loss, hearing (Clic here for more details about this article) |
5/8. A non-syndromic hearing loss caused by very low levels of the mtDNA A3243G mutation.We described a patient with progressive non-syndromic hearing loss (NSHL) harboring the A3243G mutation in the mitochondrial dna (mtDNA). Muscle biopsy showed scattered ragged-red, cytochrome c oxidase negative fibers, whereas the biochemical analysis of the mitochondrial respiratory chain complexes was normal. Restriction fragment length polymorphism (RFLP) analysis showed A3243G mtDNA transition, present at very low in patient's muscle (3%) and in urinary sediments (1%), and not detectable in blood and buccal mucosa. The patient was submitted to a bilateral cochlear implantation with post-operative excellent hearing and communicative outcomes. Our findings indicate that A3243G mutation may be responsible both for SHL and NSHL, may be depending on the levels of mutated mtDNA. patients with hearing loss due to mtDNA mutations should be considered as good candidates for cochlear implantation.- - - - - - - - - - ranking = 20.582016251765keywords = hearing loss, hearing (Clic here for more details about this article) |
6/8. Successful heart failure therapy in mitochondrial disorder with noncompaction cardiomyopathy.OBJECTIVE: Effective heart failure therapy with angiotensin-converting enzyme inhibitors and beta-blockers in a patient with mitochondrial disorder and asymptomatic previously stable hypertrophic cardiomyopathy and left ventricular noncompaction (NCCMP) has not been reported. CASE REPORT: In a 58-year-old male with juvenile seizures, impaired hearing, recurrent pancreatitis, diabetes, recurrent emesis and diarrhea, discrete weakness for hip flexion, general wasting, and reduced tendon reflexes, elevated muscle-enzymes, abnormal lactate-stress-test, and mitochondrial dysfunction on muscle biopsy, mitochondrial disorder was diagnosed at age 51 year. echocardiography revealed myocardial thickening and NCCMP. Cardiac abnormalities did not progress upon repeated follow-ups. At age 57 year he developed acute heart failure during respiratory infection. echocardiography additionally revealed reduced left ventricular systolic function, and a restrictive filling pattern. Within seven weeks of therapy with ramipril (2.5 mg/day) and bisoprolol (1.25 mg/day) the restrictive filling pattern disappeared and fractional shortening normalized. CONCLUSION: This case shows that heart failure in a patient with mitochondrial disorder and previously stable hypertrophic cardiomyopathy and NCCMP promptly resolves under therapy with angiotensin-converting enzyme inhibitors and beta-blockers.- - - - - - - - - - ranking = 1keywords = hearing (Clic here for more details about this article) |
7/8. association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation.In this paper, we describe a distinct clinical subtype of 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria is a group of different metabolic disorders biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. We performed biochemical and genetic investigations, including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydratase activity, cardiolipin levels, OPA3 gene analysis and measurement of the oxidative phosphorylation in four female patients with 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria type I, barth syndrome, and Costeff syndrome were excluded as the activity of 3-methylglutaconyl-CoA hydratase, the cardiolipin levels, and molecular analysis of the OPA3 gene, respectively, showed no abnormalities. The children presented with characteristic association of hearing loss and the neuro-radiological evidence of leigh disease. They also had neonatal hypotonia, recurrent lactic acidemia, episodes with hypoglycemia and severe recurrent infections, feeding difficulties, failure to thrive, developmental delay, and progressive spasticity with extrapyramidal symptoms. Our patients were further biochemically characterized by a mitochondrial dysfunction and persistent urinary excretion of 3-methylglutaconic acid.- - - - - - - - - - ranking = 3.2636693752942keywords = hearing loss, hearing (Clic here for more details about this article) |
8/8. Maternally inherited diabetes and deafness in a North American kindred: tips for making the diagnosis and review of unique management issues.CONTEXT: Mutations in mitochondrial dna are rare etiologies of adult-onset diabetes mellitus (DM) that merit identification to 1) prevent iatrogenic lactic acidosis, 2) prompt appropriate screening of affected patients and their families, 3) provide genetic counseling, and 4) provide an opportunity to investigate strategies for preventing diabetes. OBJECTIVE: The objective of this study is to raise awareness of this rare form of adult-onset nonobese DM so that these patients are identified and provided with appropriate care. patients: We describe a kindred in which four of seven siblings have adult-onset DM and sensorineural hearing loss with a confirmed genetic mutation at position 3243 in the tRNA. Two other siblings in this kindred demonstrate different phenotypes of mitochondrial disease. INTERVENTION: The proband was treated with coenzyme Q10 for 1 yr. OUTCOME MEASURES: Outcome measures included stress thallium exercise testing and audiometry testing. RESULTS: After 1 yr of treatment of with coenzyme Q10, repeat stress thallium testing demonstrated improvement in the exercise tolerance of the proband from 7-12 min. audiometry testing did not demonstrate a change in the rate of hearing decline. CONCLUSION: Maternally inherited diabetes and deafness is a rare cause of DM that is important to diagnose because of the unique management issues and associated comorbidities. This work highlights clues to the identification of this rare monogenic form of adult- onset diabetes.- - - - - - - - - - ranking = 14.32769838055keywords = sensorineural hearing loss, sensorineural hearing, sensorineural, hearing loss, hearing (Clic here for more details about this article) |