Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders with ataxia and dysarthria as early and dominant signs. In ADCA type II, retinal degeneration causes severe visual impairment. ADCA type II has recently been mapped to chromosome 3p by three independent groups. In the family with ADCA type II studied here, the disease has been mapped to chromosome 3p12-p21.1. Histochemical examination of muscle biopsies in 5 cases showed slight neurogenic atrophy and irregular lobulated appearance or focal decreases of enzyme activity when staining for NADH dehydrogenase, succinic dehydrogenase and cytochrome oxidase. Ragged-red fibres were scarce. Electron microscopic examination showed uneven distribution of mitochondria with large fibre areas devoid of mitochondria and/or large subsarcolemmal accumulations of small rounded mitochondria, and frequent autophagic vacuoles. These vacuoles contained remnants of multiple small rounded organelles, possibly mitochondria, and had a remarkably consistent ultrastructural appearance. Biochemical investigation of mitochondrial function showed reduced activity of complex IV and slightly reduced activity of complex I in the respiratory chain in a severely affected child while no abnormalities were found in his affected uncle.
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PMID:Muscle morphology and mitochondrial investigations of a family with autosomal dominant cerebellar ataxia and retinal degeneration mapped to chromosome 3p12-p21.1. 899 9

Two siblings (one man, one woman), presenting with diarrhea, severe weight loss peripheral neuropathy, ophthalmoparesis, asymptomatic leukoencephalopathy were diagnosed as a new cases of Mitochondrial Neuro Gastro Intestinal Encephalomyopathy syndrome (MNGIE). Hirano (1994) defined four criteria for the diagnostic: peripheral neuropathy, ophthalmoparesis, gastro intestinal dysmotility, muscle biopsy with histologic features of mitochondrial myopathy (ragged-red fibers, muscle fibers with increased succinate deshydrogenase stain or ultra structurally abnormal mitochondria). In a review of the literature, we found 31 cases with MNGIE. With our two cases, we study this group of 33 patients. First symptoms begin about 13.5 years with a median of 10 years and extremes for 1 to 32 years. The first signs are gastro intestinal symptoms (recurrent nausea, vomiting or diarrhea with intestinal dysmotility) in 22 cases, an ophthalmoparesia in 4 cases, intestinal and ocular signs in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case. During the evolution, besides the cardinal signs, the following features have been observed with a variable frequency: hearing loss, short stature, facial palsy, dysphonia, dysarthria, sweating, orthostatic hypotension, bladder dysfunction, hepatomegalia, The laboratory features are: abnormal Nerve Condition Studies/EMG compatible with a sensory motor neuropathy, lactic acidosis, mitochondrial respiratory chain defect (essentially complex IV deficiency, complex I deficiency or multiple complex defect), MRI leukodystrophy, elevated CSF protein, heart block, ragged-red fibers or increased SDH stain. The prognosis is poor, due to a severe weight loss bordering on cachexia 13 patients died with a mean age of 28.5 years (median 24 years, extreme 3 years to 51 years). The prognosis seems to be worsened by a young age of onset. The 33 patients belong to 19 families with 7 cases of consanguinity. 25 patients had a brother, a sister or a cousin affected. The study of these families is compatible with an autosomic recessive transmission, suggesting a pathology of the nuclear genomi, probably impliying the control of the mitochondrial DNA replication. In fact, in 13 cases, a study of the mt DNA was realized: multiple deletions were founded in 6 cases, multiples mutations in one case, unique mutation in 1 case. In 5 cases ther was no evidence of abnormality. These precise etiology and pathophysiologic significance of the mt DNA deletions, and the heterogeneity of the modifications of the mt DNA remain unknown. However, the possibility of various phenotypes for a same genotype or inversely is known in mitochondriopathies.
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PMID:[MNGIE syndrome in 2 siblings]. 968 18

The protean manifestations of a novel maternally inherited point mutation of the mitochondrial genome are reported. The proband showed isolated, spastic paraparesis. A brother, who had suffered from a multisystem progressive disorder, ultimately died of cardiomyopathy. Another brother is healthy. The proband's mother showed truncal ataxia, dysarthria, severe hearing loss, mental regression, ptosis, ophthalmoparesis, distal cyclones, and diabetes mellitus. A muscle biopsy performed in the proband failed to show the morphological abnormalities typical of mitochondrial disorders; the activities of respiratory chain complexes were normal. However, complex I and IV activities were low in the muscle homogenate of the affected mother and brother. Sequence analysis of mtDNA showed a heteroplasmic mutation of the tRNA(Ile) gene (G4284A). The mutation load was approximately 55%, 80%, and 90% in the muscle mtDNA of the proband, his mother, and his affected brother, respectively. Mutation was undetected in the healthy brother, as well as in 100 control samples. Several cybrid clones containing homoplasmic mutant mtDNA from the proband showed significant reductions of complex IV activity and maximum oxygen consumption rate, compared with homoplasmic wild-type clones derived from the same subject.
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PMID:Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. 1178 91

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency.
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PMID:Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy. 3065 93