Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162671 (MELAS)
 587 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Point mutations in mitochondrial DNA, as found in MELAS, MERRF, NARP and other syndromes, are inherited via the maternal lineage. Genetic counselling can be beneficial, but prenatal diagnosis is not advantageous in these syndromes. Empirical data about the recurrence risk can be applied in Leber disease (LHON). Mitochondrial disorders not associated with a point mutation have a sporadic nature (large deletions/duplications in mitochondrial DNA) or are transmitted according to Mendelian laws. Autosomal dominant inheritance is likely to be found in disorders with depletion of mitochondrial DNA. X-linked mode of inheritance is seen in Menkes disease, Barth syndrome, and in deficiencies of the E1 alpha subunit of the pyruvate dehydrogenase complex. Mutation analysis or linkage studies can be applied for carrier detection and prenatal diagnosis in these three types of mitochondriopathies. The majority of the disorders with a disturbed mitochondrial energy metabolism are likely inherited in an autosomal recessive mode. Prenatal diagnosis can be performed in the cases of cytochrome c oxidase and NADH dehydrogenase deficiencies in chorionic villi in selected families.
 ...
PMID:Genetic counselling and prenatal diagnosis in disorders of the mitochondrial energy metabolism. 888 81

An Argentine male child died at 4.5 years of age of a lethal mitochondrial disease associated with a MELAS mutation and a Barth syndrome-like presentation. The child had severe failure to thrive from the early months and for approximately two years thereafter. In addition, the patient had severely delayed gross motor milestones, marked muscle weakness, and dilated cardiomyopathy that progressed to congestive heart failure. He also had persistently elevated urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids and low blood levels of cholesterol. Detailed histopathologic evaluation of the skeletal muscle biopsy showed high activity of succinate dehydrogenase, a generalized decrease of COX activity, and abundant ragged-red fibers. Electron microscopic studies revealed multiple mitochondrial abnormalities in lymphocytes and monocytes, in the striated muscle, and in the postmortem samples (muscle, heart, liver, and brain). Biochemical analysis showed a pronounced and constant lactic acidosis, and abnormal urinary organic acid excretion (unchanged in the fasting and postprandial states). In addition, in CSF there was a marked increase of lactate and beta-hydroxybutyrate (beta-HOB) and also a high systemic ratio beta-HOB/acetoacetate. Enzymatic assay of the respiratory chain in biopsied muscle showed 10% of complex I activity and 24% of complex IV activity compared with controls. Molecular studies of the mitochondrial genome revealed an A to G mutation at nucleotide pair 3243 in mitochondrial DNA, a well-known pathogenetic mutation (MELAS mutation) in all the patient's tissues and also in the blood specimens of the probands mother and sibs (4 of 5). The diagnosis of MELAS mutation was reinforced by the absence of an identifiable mutation in the X-linked G4.5 gene of the propositus. The present observation gives additional evidence of the variable clinical expression of mtDNA mutations in humans and demonstrates that all clinical variants deserve adequate investigation to establish a primary defect. It also suggests adding Barth-like syndrome to the list of phenotypes with the MELAS mutation.
 ...
PMID:Barth's syndrome-like disorder: a new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation). 1124 64