Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain lesions exhibited on MRI and CT scan in 2 patients with mitochondrial encephalomyelopathy representing Leigh syndrome were improved by administration of dichloroacetate (DCA). One patient had pyruvic acid dehydrogenase complex (PDHC) deficiency, the other had complex I deficiency. The efficacy of DCA was transient in the patient with the PDHC deficiency, lasting for about 2.5 months. The patient died at the age of 6, about 2 years after the initiation of DCA treatment. DCA administration was started in the patient with complex I deficiency when he was 15 months old and it is still effective at his present age of 24 months. His motor ability is developing, and he could walk without support at the age of 19 months. DCA administration should be tried in patients with mitochondrial diseases.
 ...
PMID:Improvement of lesions shown on MRI and CT scan by administration of dichloroacetate in patients with Leigh syndrome. 874 51

We administered sodium dichloroacetate (DCA), which reduces the circulating lactate and pyruvate concentrations by stimulating the activity of the pyruvate dehydrogenase complex (PDHC), to three children with mitochondrial encephalomyelopathy. Significant clinical, biochemical and radiologic improvements were obtained following DCA therapy (approximately 30 mg/kg per day, divided into three doses). All three patients had non-pyruvate dehydrogenase complex (PDHC) deficiencies: two exhibited Leigh syndrome (complex I deficiency and unknown etiology), and one abnormal myelination (multienzyme deficiency), demonstrated on magnetic resonance imaging (MRI). The lactic and pyruvic acid concentrations in serum and cerebrospinal fluid (CSF) were decreased significantly by the oral DCA treatment. The lactic acid peak on MR spectroscopy also markedly decreased in parallel with the CSF level. In addition, the brain lesions observed on MRI were improved in all patients. No exacerbation was observed in any of the patients, who have been followed-up more than 21 months following the DCA therapy. These results suggest that DCA therapy should be considered in all patients with a mitochondria-related enzyme deficiency.
 ...
PMID:Clinical and radiologic improvements in mitochondrial encephalomyelopathy following sodium dichloroacetate therapy. 944 Jul 97

We report a patient presenting with severe muscular impairment and chronic intestinal pseudo-obstruction (CIP) at the age of eight months. Due to the aggravated symptoms, assisted ventilation, an ileostomy and total parenteral nutrition were required. Later on, the patient developed a locked-in syndrome (Leigh's subacute necrotising encephalomyelopathy) and finally died due to recurrent pneumonia and chronic renal failure. The assessment of muscle biopsies revealed a moderate single-fibre type II atrophy, a variation of muscle fibre calibre with focal fatty degeneration and a decreased reactivity of cytochrome-c oxidase. Although ragged red fibres had not been found, mitochondrial enzyme activities were markedly decreased with the lowest residual activity detected for NADH:Q1 oxidoreductase and NADH:O2 oxidoreductase (complex I deficiency), thereby confirming the diagnosis of mitochondrial myopathy. A molecular genetic analysis could not identify known mutations of mitochondrial DNA. Gastrointestinal full-thickness biopsies revealed myenteric hypoganglionosis of the colon and stomach and hyperplasia of the submucosal plexus of the ileum. Some of the intestinal smooth muscle cells displayed bulbous protrusions filled with lateralised mitochondria. Mitochondrial myopathies are known to be associated with a variety of clinical syndromes including CIP. However, in contrast to previous reports in which CIP has been attributed to visceral intestinal myopathies, the present case is characterised by neuronal intestinal malformations. Therefore, a mitochondrial myopathy associated with CIP requires a subtle assessment of both the intestinal smooth muscle and the enteric nervous system to identify the underlying pathology.
 ...
PMID:Mitochondrial myopathy (complex I deficiency) associated with chronic intestinal pseudo-obstruction. 1293 6

Leigh disease (LD) is one of the clinical phenotypes of mitochondrial OXPHOS disorders and also known as sub-acute necrotizing encephalomyelopathy. The disease has an incidence of 1 in 77,000 live births. Symptoms typically begin early in life and prognosis for LD patients is poor. Currently, no clinically effective treatments are available. Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. In this study we used the Ndufs4 knockout (Ndufs4(-/-)) mouse, a model of mitochondrial complex I deficiency. Ndusf4(-/-) mice exhibit progressive neurodegeneration, which closely resemble the human LD phenotype. When dissecting behavioral abnormalities in animal models it is of great importance to apply translational tools that are clinically relevant. To distinguish gait abnormalities in patients, simple walking tests can be assessed, but in animals this is not easy. This study is the first to demonstrate automated CatWalk gait analysis in the Ndufs4(-/-) mouse model. Marked differences were noted between Ndufs4(-/-) and control mice in dynamic, static, coordination and support parameters. Variation of walking speed was significantly increased in Ndufs4(-/-) mice, suggesting hampered and uncoordinated gait. Furthermore, decreased regularity index, increased base of support and changes in support were noted in the Ndufs4(-/-) mice. Here, we report the ability of the CatWalk system to sensitively assess gait abnormalities in Ndufs4(-/-) mice. This objective gait analysis can be of great value for intervention and drug efficacy studies in animal models for mitochondrial disease.
...
PMID:Gait analysis in a mouse model resembling Leigh disease. 2636 24