Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0751651 (mitochondrial disease)
 1,844 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpers-Huttenlocher syndrome, considered a mitochondrial disease, combines encephalopathy and liver failure. An 11-year-old boy with Alpers-Huttenlocher syndrome underwent conventional MR imaging, diffusion-weighted imaging, and proton MR spectroscopy. Diffusion-weighted imaging showed cytotoxic edema interpreted as acute-phase encephalopathy. MR spectroscopy revealed a lactate peak in the cortex that appeared abnormal on diffusion-weighted images, possibly representing respiratory deficiency with anaerobic metabolism. MR spectroscopy proved to be more sensitive regarding lactate detection than did neurometabolic examination of serum and CSF. A reduced N-acetylaspartate-creatine ratio was detected in both the cortex that appeared abnormal and the cortex that appeared normal on the diffusion-weighted images, indicating neuronal damage that was widespread, even beyond the boundaries of conventional MR imaging changes.
 ...
PMID:MR spectroscopic findings in a case of Alpers-Huttenlocher syndrome. 1222 90

We describe two children carrying an inherited T899C mutation in the mitochondrial ATPase 6 gene with mild encephalopathy and normal postnatal growth followed by tall stature and obesity. No familial tall stature, endocrine anomaly or advanced skeletal age were present. Failure to thrive is a characteristic finding in most patients with a mitochondrial disease. Our observations suggest that children with encephalomyopathy, even in the presence of a significant clinical overgrowth, should be screened for a possible defect in oxidative phosphorylation.
 ...
PMID:Tall stature and progressive overweight in mitochondrial encephalopathy. 1470 24

Leber hereditary optic neuropathy (LHON)/pediatric onset dystonia is associated with a G to A transition at nucleotide position (np) 14459, within the mitochondrial DNA (mtDNA)-encoded ND6 gene. This mutation has been reported in families presenting with LHON alone, LHON plus dystonia, or pediatric dystonia with typical age of onset less than 5 years. The mutation changes a moderately conserved alanine to a valine at amino acid residue 72, which is within the most evolutionarily conserved region of the ND6 protein. Pediatric onset disease is associated with basal ganglia dysfunction, spasticity, and encephalopathy. We report a family with G14459A mtDNA mutation and a broad spectrum of clinical manifestation. The proband was a 3-year-old girl with anarthria, dystonia, spasticity, and mild encephalopathy. MRI of the brain demonstrated bilateral, symmetric basal ganglia lucencies associated with cerebral and systemic lactic acidosis. Her maternal first cousin presented with a new onset limp and mild hemiparesis along with similar MRI findings with a much milder phenotype. Additional investigation of the family members with the mutation has revealed both asymptomatic and symptomatic individuals with variable clinical and laboratory features of mitochondrial disease. This study re-emphasizes the heterogeneous clinical manifestation of homoplasmic G14459A mtDNA mutation even within the same family, and supports the hypothesis that nuclear genes may play a role in modifying the clinical expression of mitochondrial disease. Published 2003 Wiley-Liss, Inc.
 ...
PMID:Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation. 1473 85

One challenge in the molecular diagnosis of mitochondrial DNA (mtDNA) disorders is detection of a low percentage of mutant heteroplasmy. We report a patient who had a delayed molecular diagnosis of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome due to the complication of an extensive family history of another neuromuscular disease, Duchenne muscular dystrophy, and the failure to detect a low proportion of mutant A3243G mtDNA with a polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP)/ethidium bromide detection method. Using an improved, more sensitive allele-specific oligonucleotide (ASO) radioactive dot-blot hybridization method, a low degree of A3243G heteroplasmy was detected in several tissues from this patient. This case underscores the importance of a sensitive mutation detection method and the need for a search for mtDNA mutations if the patient's clinical symptoms suggest a mitochondrial disorder despite the family background of another neuromuscular disease.
 ...
PMID:A mitochondrial DNA mutation in a patient with an extensive family history of Duchenne muscular dystrophy. 1522 88

Physicians must be able to recognize stroke caused by a mendelian or mitochondrial disorder. Some genetic disorders such as sickle cell anemia and Fabry disease have proven disease-specific treatments, whereas others have no effective treatment, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Proper diagnosis of a genetic disorder has prognostic value and prevents patient exposure to unnecessary and potentially harmful therapeutic agents and diagnostic tests. This article reviews the clinical and genetic features of some mendellan and mitochondrial disorders associated with ischemic stroke, hemorrhagic stroke, and cerebrovascular malformations.
 ...
PMID:Genetics of cerebrovascular disorders. 1566 40

We present here a patient with muscle fatigue and poor growth since the age of 6 y. The diagnosis of a mitochondrial disease was based on the presence of ragged red fibers in the muscle biopsy and on a combined defect of mitochondrial DNA-encoded respiratory enzymes. Epilepsia partialis continua with stroke-like episodes appeared 2 mo before death at the age of 18 and prompted a search for mitochondrial DNA mutations associated with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes. Minisequencing of the patient's DNA samples revealed a heteroplasmic T3271C mutation with a 78-94% mutation load in her fibroblasts or autopsy-derived tissue samples. This is the ninth reported non-Japanese patient with T3271C mutation. Our patient shows that despite very high proportion of mutant mtDNA, the T3271C mutation can give rise to mild symptoms in childhood and to a rapid terminal phase that simulates encephalitis.
 ...
PMID:A juvenile case of MELAS with T3271C mitochondrial DNA mutation. 1600 33

Disease-causing mutations in mitochondrial DNA (mtDNA) are typically heteroplasmic and therefore interpretation of genetic tests for mitochondrial disorders can be problematic. Detection of low level heteroplasmy is technically demanding and it is often difficult to discriminate between the absence of a mutation or the failure of a technique to detect the mutation in a particular tissue. The reliable measurement of heteroplasmy in different tissues may help identify individuals who are at risk of developing specific complications and allow improved prognostic advice for patients and family members. We have evaluated Pyrosequencing technology for the detection and estimation of heteroplasmy for six mitochondrial point mutations associated with the following diseases: Leber's hereditary optical neuropathy (LHON), G3460A, G11778A, and T14484C; mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), A3243G; myoclonus epilepsy with ragged red fibers (MERRF), A8344G, and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP)/Leighs: T8993G/C. Results obtained from the Pyrosequencing assays for 50 patients with presumptive mitochondrial disease were compared to those obtained using the commonly used diagnostic technique of polymerase chain reaction (PCR) and restriction enzyme digestion. The Pyrosequencing assays provided accurate genotyping and quantitative determination of mutational load with a sensitivity and specificity of 100%. The MELAS A3243G mutation was detected reliably at a level of 1% heteroplasmy. We conclude that Pyrosequencing is a rapid and robust method for detecting heteroplasmic mitochondrial point mutations.
 ...
PMID:Accurate detection and quantitation of heteroplasmic mitochondrial point mutations by pyrosequencing. 1622 98

Mitochondrial diseases represent a heterogeneous group of disorders associated with a wide array of clinical manifestations. The presentation of patients with mitochondrial pathology largely depends upon the dysfunction of organ systems with large metabolic/energy requirements, including cardiac, neurologic, and musculoskeletal. In particular, mitochondrial myocardial disease can be progressive resulting in congestive heart failure and end-stage heart disease. This article reviews the role of heart transplantation for a particular variant of mitochondrial disorder, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, and discusses perioperative management issues related to transplantation for mitochondrial cardiomyopathies.
 ...
PMID:Heart transplantation for progressive cardiomyopathy as a manifestation of MELAS syndrome. 1636 83

Mitochondrial encephalopathy, lactic acidosis with stroke-like episodes (MELAS) is a rare mitochondrial disorder that affects adults. MELAS syndrome can mimic cerebrovascular disease, encephalitis or toxic-metabolic encephalopathy. The authors reported two patients who presented with auditory symptoms before the onset of encephalopathy and stroke-like episodes. The first patient was a 28 year-old man, who presented with acute sensorineural hearing loss (SNHL) followed by headache, left hemiparesis and generalized tonic-clonic seizure. CT scan of the brain showed hypodensity lesion at the tip of right temporooccipital region. Audiogram and brainstem auditory evoked potential (BAEP) showed abnormal conduction of left brainstem auditory pathway. MRI of the brain showed a lesion involving gray and white matters of the right occipital, parietal and temporal lobes. The distribution of the lesions was not compatible with distribution of arterial supply. MRA was normal. The second patient was a 56 year-old woman with a one-year history of hearing loss. The audiogram revealed bilateral SNHL. A few days before admission, her hearing was acutely deteriorated She could not understand a conversation while she could communicate by writing. CT scan of the brain showed hypodensity in both temporal lobes and MRI revealed lesions in the same area. Pure tone audiogram showed moderate SNHL but BAEP was normal. One week later, she developed global dysphasia and generalized tonic-clonic seizure. Both patients had elevated cerebrospinal fluid and serum lactate: pyruvate ratio. Polymerase chain reaction-restriction fragment length polymorphism disclosed A3243G mtDNA mutation in the blood in the first patient and in muscle biopsy in the second patient. Ubiquinone supplement was prescribed The auditory symptoms in combination with stroke-like episode in supratentorium are important clues to diagnose MELAS syndrome.
 ...
PMID:Auditory symptoms: a critical clue for diagnosis of MELAS. 1647 Nov 25

Mitochondrial respiratory chain disorders are clinically and genetically heterogeneous. There are several mitochondrial DNA (mtDNA) point mutations responsible for common mitochondrial diseases such as mitochondrial encephalopathy, lactic acidosis, stroke-like events, myoclonic epilepsy and ragged red fibers, neuropathy, ataxia, retinitis pigmentosa, and Leber's hereditary optic neuropathy. As a result of the clinical overlap, it is usually necessary to analyze more than one mutation for a patient suspected of a mitochondrial disorder. Molecular diagnosis is often performed using polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) analysis of the most likely point mutations. However, this method is time-consuming and often produces problems associated with incomplete restriction enzyme digestion. In addition, PCR/RFLP analysis may not be able to detect a low percentage of heteroplasmy. For a more effective method of diagnosing mtDNA disorders, we have developed a multiplex PCR/ allele-specific oligonucleotide (ASO) dot blot hybridization method to simultaneously analyze 11 point mutations. The PCR products from a DNA sample containing a homoplasmic wild-type or mutant mtDNA sequence will hybridize to either the wild-type or the mutant ASO probe. The PCR products of a heteroplasmic DNA sample will hybridize to both wild-type and mutant ASO probes. This PCR/ASO method allows the detection of low percentage mutant heteroplasmy.
 ...
PMID:Molecular analysis of mitochondrial DNA point mutations by polymerase chain reaction. 1691 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>