Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the last decade, mitochondrial diseases were shown not to be rare but to represent an important group of metabolic disorders. Defects are caused by mutations either located in nuclear genes or in mitochondrial genes. Nuclear gene defects are found in complex IV deficient and complex I deficient patients. Deficiencies of complex II are extremely rare. Different phenotypes are associated with complex IV deficiency, including a neonatal form, cardio-encephalomyopathy in young infants, Leigh syndrome, and pure myopathy. Mutations can be found in the complex IV assembly genes, such as the SURF-1 gene and the SCO2 gene. Different phenotypes are also found in complex I deficient patients and include a neonatal form, Leigh syndrome, pure myopathy, pure cardiomyopathy or multiple-system involvement. In some disorders, the mitochondrial DNA abnormalities are caused by a nuclear gene defect (Alpers-Huttenlocher syndrome, autosomal dominant multiple mitochondrial DNA deletion syndrome, and MNGIE syndrome). Since 1988, more then 70 different mutations were reported in the mitochondrial DNA. Some point mutations are associated with a specific phenotype, others have a wide range of clinical symptoms. We expect that many more mitochondrial DNA mutations will be identified in the future. The number of mutations in nuclear genes will also increase, especially since progress has been made in techniques used for identification of nuclear genes (microcell transfer).
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PMID:Mitochondrial cytopathies and neuromuscular disorders. 1109 88

Mitochondrial dysfunction of the energy generating system was suggested in two infants with progressive infantile poliodystrophy characterised by hypotonia, refractory epilepsy, visual impairment, psychomotor retardation, profound brain atrophy, hepatopathy, and increased levels of lactate in blood and cerebrospinal fluid. Histochemical and electron microscopic analyses of liver biopsies revealed cytochrome c oxidase deficiency, microvesicular steatosis, and enormous multiplication of mitochondria of various sizes. In the first patient, the quantitative Southern blot analyses in tissues obtained at autopsy demonstrated reduced content of mtDNA in the liver, brain, and fibroblasts (11 %, 15 %, and 25 % of the mean values in controls) while a normal content of mtDNA was found in muscle and heart. In the second patient, a reduced content of mtDNA was found in the muscle, liver, and brain (15 %, 10 %, and 30 %, respectively, of the mean values in controls). Biochemical studies in the first patient revealed decreased activities of all respiratory chain complexes except complex II in isolated liver mitochondria and decreased amounts of respiratory chain complexes I, III, IV and ATP synthase in liver and frontal cortex, but not in muscle, heart, and fibroblasts. In conclusions, mtDNA depletion associated with Alpers syndrome may be tissue specific.
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PMID:Mitochondrial DNA depletion in Alpers syndrome. 1532 60

Failure to thrive, feeding difficulties, variable forms of infantile epilepsy or psychomotor developmental delay and hypotonia were the most frequent clinical disease presentations in eight children with combined oxidative phosphorylation enzyme complex deficiencies carrying mutations in the polymerase gamma (POLG1) gene. Five out of eight patients developed severe liver dysfunction during the course of the disease. Three of these patients fulfilled the disease criteria for Alpers syndrome. Most children showed deficiencies of respiratory chain enzyme complexes I and III, in combination with complex II, complex IV and/or PDHc in muscle, whereas in fibroblasts normal enzyme activities were measured. All children carried homozygous or compound heterozygous mutations in the POLG1 gene, including two novel mutations in association with mtDNA depletion. Conclusion We suggest performing POLG1 mutation analysis in children with combined oxidative phosphorylation deficiencies in muscle, even if the clinical picture is not Alpers syndrome.
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PMID:Multiple oxidative phosphorylation deficiencies in severe childhood multi-system disorders due to polymerase gamma (POLG1) mutations. 1695