Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial DNA depletion is a quantitative disorder of mtDNA, characterized by tissue-specific reductions in mtDNA copy number, that presents in infancy or early childhood. It is most likely transmitted as an autosomal recessive trait, although about half of the described cases are sporadic. To estimate its prevalence we measured relative mtDNA copy number (mtDNA: 18S rDNA ratio) by Southern blot analysis in muscle biopsy samples from all children with compatible histories referred between 1983 and 1994. Of the 304 biopsies evaluated, 54 met the study criteria. We found 6 patients (2 male, 4 female) with mtDNA depletion (relative mtDNA copy number 7.9-33.2% of control). Their clinical course and findings were heterogeneous, however all but one manifested weakness, hypotonia, and developmental delay. Clinical severity was not obviously related to the degree of mtDNA depletion. No patient had ragged-red fibers, although 2 had a lipid storage myopathy. Immunofluorescence with antibodies to double-stranded DNA, COX IV, and COX II demonstrated homogeneously reduced reactivity to all three antibodies compared with control. mtDNA depletion may be a relatively common neurogenetic disorder of infancy and early childhood and should be considered in children with unexplained weakness, hypotonia, or developmental delay.
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PMID:Mitochondrial DNA depletion: prevalence in a pediatric population referred for neurologic evaluation. 873 3

Ethylmalonic encephalopathy (EE) is a rare metabolic disorder with an autosomal recessive mode of inheritance that is clinically characterized by neuromotor delay, hyperlactic acidemia, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. Increased urinary levels of ethylmalonic acid and methylsuccinic acid are the main biochemical features of the disorder. We report on two patients affected by EE who showed different clinical and neuroradiological patterns. Patient 1 presented with a chronic clinical course characterized by very slow neuromotor deterioration, ataxia, and dysarthria. In contrast, patient 2 had an acute neonatal onset with severe neuromotor retardation, severe generalized hypotonia, and intractable seizures. Neuroradiological follow-up of patient 1 detected a diffuse hyperintensity on the T2 images at the basal ganglia which remained stable during a period of four years. Patient 2, in contrast, showed a rapid process of cerebral, and in part, cerebellar atrophy. On the basis of our observations, we reviewed the data published in the literature and tried to delineate the natural history of EE, which appears to be characterized by a wide spectrum of severity in the clinical course. No reports on neuroradiological follow-up of EE patients are available in the literature with which to compare our data. Finally, both patients showed a muscle COX deficiency. The pathogenetic implications of such a biochemical finding will be also discussed.
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PMID:Ethylmalonic encephalopathy: further clinical and neuroradiological characterization. 1238 64

Mitochondrial DNA depletion syndrome (MDS) is characterized by a reduction in mtDNA copy number and has been associated with mutations in eight nuclear genes, including enzymes involved in mitochondrial nucleotide metabolism (POLG, TK2, DGUOK, SUCLA2, SUCLG1, PEO1) and MPV17. Recently, mutations in the RRM2B gene, encoding the p53-controlled ribonucleotide reductase subunit, have been described in seven infants from four families, who presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis. All children died before 4 months of age. We sequenced the RRM2B gene in three unrelated cases with unexplained severe mtDNA depletion. The first patient developed intractable diarrhea, profound weakness, respiratory distress, and died at 3 months. The other two unrelated patients had a much milder phenotype and are still alive at ages 27 and 36 months. All three patients had lactic acidosis and severe depletion of mtDNA in muscle. Muscle histochemistry showed RRF and COX deficiency. Sequencing the RRM2B gene revealed three missense mutations and two single nucleotide deletions in exons 6, 8, and 9, confirming that RRM2B mutations are important causes of MDS and that the clinical phenotype is heterogeneous and not invariably fatal in infancy.
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PMID:Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene. 1850 29

Cytochrome c oxidase 20 (COX20)/FAM36A encodes a conserved protein that is important for the assembly of COX, complex IV of the mitochondrial respiratory chain. A homozygous mutation (p.Thr52Pro) in COX20 gene has been previously described to cause muscle hypotonia and ataxia. In this study, we describe two patients from a non-consanguineous family exhibiting autosomal recessive sensory-dominant axonal neuropathy and static encephalopathy. The whole-exome sequencing analysis revealed that both patients harbored compound heterozygous mutations (p.Lys14Arg and p.Trp74Cys) of COX20 gene. The pathogenicity of the variants was further supported by morphological alternations of mitochondria observed in sural nerve and decreased COX20 protein level of peripheral blood leucocytes derived from the patients. In conclusion, COX20 might be considered as a candidate gene for the complex inherited disease. This observation broadens the clinical and genetic spectrum of COX20-related disease. However, due to the limitation of a single-family study, additional cases and studies are definitely needed to further confirm the association.
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PMID:Observation of novel COX20 mutations related to autosomal recessive axonal neuropathy and static encephalopathy. 3107 2