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)

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), one of the most common mitochondrial multisystemic diseases, is most commonly associated with an A-to-G transition at nucleotide position 3243 (A3243G) in mitochondrial DNA. We studied 34 individuals harboring the A3243G mutation for up to 7 years; 17 had the full MELAS phenotype and 17 who were classified as "carrier relatives" because they were either asymptomatic or had some symptoms suggestive of mitochondrial disease but no seizures or strokes. Using the sensitive real-time polymerase chain reaction to quantify the A3243G mutation, we confirmed that the percent mutation decreases progressively in DNA isolated from blood: the average percent decrease was 0.5% per year for fully symptomatic patients and 0.2% per year for oligosymptomatic carrier relatives. We also correlated mutant loads with functional status estimated by the Karnofksky score: even though the mutation load decreases, the level of functioning worsens in fully symptomatic patients, whereas the level of functioning of carrier relatives remains largely unchanged. This study suggests that A3243G mutant load in DNA isolated from blood is neither useful for prognosis nor for functional assessment.
 ...
PMID:Longitudinal changes of mtDNA A3243G mutation load and level of functioning in MELAS. 1925 45

Mitochondrial myopathy may manifest either as isolated myopathy or as a neuromuscular multisystemic disease and is caused by genetic defects in the mitochondrial genome resulting in respiratory chain disorders. MELAS, which is characterised by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes due to gene mutations in the mitochondrial DNA (adenine-to-guanine transition at nucleotide pair 3243, m.3243A>G), constitutes such a mitochondrial multisystemic disease. Although hypertrophied or dilated cardiomyopathy is quite common in MELAS, there have been no cardiovascular magnetic resonance (CMR)-based studies in these patients so far. This case report represents the first case in which comprehensive CMR and endomyocardial biopsy (EMB) data were obtained in the same patient with mitochondrial myopathy. Late gadolinium enhancement (LGE) imaging demonstrated a unique pattern of myocardial damage and histological work-up revealed the presence of "ragged red fibers" (conglomerates of mitochondria) in the heart tissue verifying the diagnosis of a mitochondrial cardiomyopathy as part of the underlying mitochondrial disease MELAS.
 ...
PMID:CMR gives clue to "ragged red fibers" in the heart in a patient with mitochondrial myopathy. 1934 65

Two novel mitochondrial DNA base changes were identified at both sides of the 3243A>G mutation, the most common mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). One was a 3244G>A transition in a girl with MELAS. The other was a 3242G>A transition in a girl with a mitochondrial disorder without a MELAS phenotype. Although the two base changes were adjacent to the 3243A>G mutation, they had different effects on the clinical phenotype, muscle pathology, and respiratory chain enzyme activity. Investigations of the different effects of the 3244G>A and 3242G>A base changes may provide a better understanding of tRNA dysfunction in mitochondrial disorders.
 ...
PMID:Different effects of novel mtDNA G3242A and G3244A base changes adjacent to a common A3243G mutation in patients with mitochondrial disorders. 1946 Feb 99

Mitochondrial disorders are frequently encountered inherited diseases characterized by unexplained multisystem involvement with a chronic, intermittent, or progressive nature. The objective of this paper is to describe the profile of patients with mitochondrial disorders in South Africa. Patients with possible mitochondrial disorders were accessed over 10 years. Analyses for respiratory chain and pyruvate dehydrogenase complex enzymes were performed on muscle. A diagnosis of a mitochondrial disorder was accepted only if an enzyme activity was deficient. Sixty-three patients were diagnosed with a mitochondrial disorder, including 40 African, 20 Caucasian, one mixed ancestry, and two Indian patients. The most important findings were the difference between African patients and other ethnicities: respiratory chain enzyme complexes CI+III or CII+III deficiencies were found in 52.5% of African patients, being of statistical significance (p value = 0.0061). They also presented predominantly with myopathy (p value = 0.0018); the male:female ratio was 1:1.2. Twenty-five (62.5%) African patients presented with varying degrees of a myopathy accompanied by a myopathic face, high palate, and scoliosis. Fourteen of these 25 also had ptosis and/or progressive external ophthalmoplegia. No patients of other ethnicities presented with this specific myopathic phenotype. Caucasian patients (16/20) presented predominantly with central nervous system involvement. Of the South African pediatric neurology patients, Africans are more likely to present with myopathy and CII+III deficiency, and Caucasian patients are more likely to present with encephalopathy or encephalomyopathy.
 ...
PMID:An overview of a cohort of South African patients with mitochondrial disorders. 2013 31

A 26-month-old child presented with an unusual combination of growth retardation, renal proximal tubulopathy, hypoparathyroidism, and episodic encephalopathy with fever and lethargy. Muscle biopsy revealed defects of mitochondrial respiratory chain enzyme complexes I, III, and IV, but no ragged-red fibers or cytochrome c oxidase deficient fibers. Analysis of muscle mitochondrial DNA (mtDNA) showed a heteroplasmic 7663 base pair (bp) single deletion with a perfect 10 bp direct sequence repeat at the boundaries. At age 3 years and 9 months, the child developed sepsis and acute deterioration of her encephalopathy leading to death. This case expands the phenotypic diversity of mitochondrial disorders in pediatric patients and reinforces the importance of biochemical analyses of muscle biopsies in patients suspected of having a mitochondrial disorder.
 ...
PMID:A single large-scale deletion of mtDNA in a child with recurrent encephalopathy and tubulopathy. 2022 71

Mitochondrial encephalopathy, the most common neurometabolic disorder, may be caused by mutations in approximately 100 different genes and may present with various symptoms, such as seizures, ataxia, myopathy, cognitive impairment, blindness, and stroke. Fewer than 50% of patients with mitochondrial encephalopathy receive a molecular diagnosis, primarily because of the large degree of clinical and genetic heterogeneity among patients and the limited knowledge of the genes involved in mitochondrial function. Here we review the most recent discoveries of genes associated with mitochondrial disease with variable neuropathology. All these genes have been identified via homozygosity mapping or linkage analysis; however, advances in sequencing technology indicate that the future of genetic diagnosis and disease gene discovery likely lies in high-throughput sequencing.
 ...
PMID:Recent advances in the genetics of mitochondrial encephalopathies. 2044 63

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited multisystem mitochondrial disorder. Although many molecular and cellular mechanisms have been discovered leading to mitochondrial cytopathy, the pathogenic mechanism of stroke-like episodes seen in MELAS has not been clarified yet. According to the muscle and brain pathology and vascular physiology, mitochondrial angiopathy, or endothelial dysfunction, were proposed to play an important role for developing stroke-like episodes. Based on a hypothesis of mitochondrial angiopathy theory, we use L-arginine in MELAS patients and report its usefulness. This review aims to give a general idea on the actual knowledge about the possible pathogenic mechanism of stroke-like episodes, including clinical symptoms that lead to stroke-like episodes, muscle, or brain pathology, molecular cellular functions, neuroimagings including MRI, MRS, and SPECT, and the proposed site of action of L-arginine therapy on MELAS patients. Currently, L-arginine therapy may be the most promising for the treatment of stroke-like episodes in MELAS.
 ...
PMID:MELAS and L-arginine therapy: pathophysiology of stroke-like episodes. 2064 46

Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. Magnetic resonance imaging changes may be nonspecific, such as atrophy (both general and involving specific structures, such as cerebellum), more suggestive of particular disorders such as focal and often bilateral lesions confined to deep brain nuclei, or clearly characteristic of a given disorder such as stroke-like lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White matter hyperintensities with or without associated gray matter involvement may also be observed. Across patients and discrete disease subtypes (e.g., MELAS, Leigh syndrome, etc.), patterns of these features are helpful for diagnosis. However, it is also true that marked variability in expression occurs in all mitochondrial disease subtypes, illustrative of the complexity of the disease process. The present review summarizes the role of neuroimaging in the diagnosis and characterization of patients with suspected mitochondrial disease.
 ...
PMID:The use of neuroimaging in the diagnosis of mitochondrial disease. 2081 27

An 11-year-old girl and a 25-year-old woman were both initially referred to a neurologist with 'common' neurological problems: The girl suffered from tics, and later epilepsy, and her serum lactate concentration was elevated. She had unilateral hyperintensity of the left cerebral cortex and later developed diabetes mellitus. The woman had muscle weakness, diabetes mellitus and ptosis. In both patients, the problems turned out to be an expression of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). The first patient died at 18 years of age during an epileptic seizure with severe metabolic disturbances. The second patient developed bilateral perceptive hearing loss, epilepsy and cardiomyopathy and she was repeatedly admitted to hospital with stroke-like episodes. She died at 46 years of age. Both patients had the MELAS A3243G point mutation. MELAS is a maternally inherited mitochondrial disorder. The age of onset and symptoms are highly variable, even within one family. To date there are no curative treatment options for the disease. Diagnosing MELAS is important though, for optimising the treatment of the individual symptoms and genetic counselling.
 ...
PMID:[Unexceptional symptoms as expression of MELAS]. 2108 56

The mitochondrial translation system is responsible for the synthesis of 13 proteins required for oxidative phosphorylation (OXPHOS), the major energy-generating process of our cells. Mitochondrial translation is controlled by various nuclear encoded proteins. In 27 patients with combined OXPHOS deficiencies, in whom complex II (the only complex that is entirely encoded by the nuclear DNA) showed normal activities, and mutations in the mitochondrial genome as well as polymerase gamma were excluded, we screened all mitochondrial translation factors for mutations. Here, we report a mutation in mitochondrial elongation factor G1 (GFM1) in a patient affected by severe, rapidly progressive mitochondrial encephalopathy. This mutation is predicted to result in an Arg250Trp substitution in subdomain G' of the elongation factor G1 protein and is presumed to hamper ribosome-dependent GTP hydrolysis. Strikingly, the decrease in enzyme activities of complex I, III and IV detected in patient fibroblasts was not found in muscle tissue. The OXPHOS system defects and the impairment in mitochondrial translation in fibroblasts were rescued by overexpressing wild-type GFM1, establishing the GFM1 defect as the cause of the fatal mitochondrial disease. Furthermore, this study evinces the importance of a thorough diagnostic biochemical analysis of both muscle tissue and fibroblasts in patients suspected to suffer from a mitochondrial disorder, as enzyme deficiencies can be selectively expressed.
 ...
PMID:Mutation in subdomain G' of mitochondrial elongation factor G1 is associated with combined OXPHOS deficiency in fibroblasts but not in muscle. 2111 9


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