Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial disorders have notoriously variable clinical presentations, particularly in children. A growing number of reports describe mutations in the mitochondrial DNA (mtDNA)-encoded subunits of complex I (EC 1.6.5.3) causing early-onset encephalopathy. Here, we describe two Korean siblings with childhood-onset progressive generalized dystonia and one Korean child with strokelike episodes in infancy; all three had bilateral lesions of the basal ganglia and partial deficiencies of complex I. Analysis of their mtDNA revealed a novel heteroplasmic m.10197G>A mutation (A47T) in the ND3 (NADH dehydrogenase subunit 3) gene. This study underscores the importance of screening mtDNA-encoded respiratory chain structural genes, including ND3, in pediatric patients with unexplained encephalopathies.
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PMID:A novel ND3 mitochondrial DNA mutation in three Korean children with basal ganglia lesions and complex I deficiency. 1741 73

The mutation pattern of mitochondrial DNA (mtDNA) in mainland Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) has been rarely reported, though previous data suggested that the mutation pattern of MELAS could be different among geographically localized populations. We presented the results of comprehensive mtDNA mutation analysis in 92 unrelated Chinese patients with MELAS (85 with classic MELAS and 7 with MELAS/Leigh syndrome (LS) overlap syndrome). The mtDNA A3243G mutation was the most common causal genotype in this patient group (79/92 and 85.9%). The second common gene mutation was G13513A (7/92 and 7.6%). Additionally, we identified T10191C (p.S45P) in ND3, A11470C (p. K237N) in ND4, T13046C (p.M237T) in ND5 and a large-scale deletion (13025-13033:14417-14425) involving partial ND5 and ND6 subunits of complex I in one patient each. Among them, A11470C, T13046C and the single deletion were novel mutations. In summary, patients with mutations affecting mitochondrially encoded complex I (MTND) reached 12.0% (11/92) in this group. It is noteworthy that all seven patients with MELAS/LS overlap syndrome were associated with MTND mutations. Our data emphasize the important role of MTND mutations in the pathogenicity of MELAS, especially MELAS/LS overlap syndrome.
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PMID:Mutations in mitochondrially encoded complex I enzyme as the second common cause in a cohort of Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. 2185 8

Leigh syndrome (LS) is a mitochondrial disease of infancy and early childhood, that is rarely seen in adults. The high degree of genetic and clinical heterogeneity makes LS a very complex syndrome. The clinical manifestations include neurological symptoms and various non-neurological symptoms, with different mutations differing in presentations and therapies. The m.10191T>C mutation in the mitochondrial DNA gene encoding in the respiratory chain complex I (CI) subunit of MTND3 results in the substitution of a highly conserved amino acid (p.Ser45Pro) within the ND3 protein, leading to CI dysfunction and causing a broad clinical spectrum of disorders that includes LS. Patients with the m.10191T>C mutation are rare in general, even more so in adults. In the present study, we report a family of patients with very rare adult-onset Leigh-like syndrome with the m.10191T>C mutation. The 24-year-old proband presented with seizures 6 years ago and developed refractory status epilepticus on admission. She had acute encephalopathy accompanied by lactic acidosis, symmetrical putamen and scattered cortical lesions. The video electroencephalogram suggested focal-onset seizures. She harbored the heteroplasmic m.10191T>C mutation in her blood and fibroblasts. Her aunt was diagnosed with mitochondrial disease at the age of 42, and had the heteroplasmic m.10191T>C mutation in her fibroblasts. Her aunt's son (cousin) died of respiratory failure at the age of 8, and we suspected he was also a case of LS. Furthermore, we reviewed the previously reported patients with the m.10191T>C mutation and summarized their characteristics. Recognizing the characteristics of these patients will help us improve the clinical understanding of LS or Leigh-like syndrome.
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PMID:A Chinese Family With Adult-Onset Leigh-Like Syndrome Caused by the Heteroplasmic m.10191T>C Mutation in the Mitochondrial MTND3 Gene. 3158 58