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)

Skeletal muscle hypotonia is a hallmark clinical finding in very-low-birth-weight (VLBW) human infants. Although the biochemical basis for this phenomenon is not completely understood, one hypothesis is that the phosphorylation potential is abnormally low in the skeletal muscle of these infants. Therefore, we used 31P-nuclear magnetic resonance (NMR) spectroscopy to measure phosphorus metabolites in the skeletal muscle of VLBW infants during rest and during reflex-induced muscle contractions. Compared with healthy larger infants or to adults, the total phosphorus NMR signal is lower in VLBW infants. In VLBW infants during rest, [PCr]/([PCr]+[Pi]), where PCr is phosphocreatine and brackets denote concentration, was 89% and [ATP]/[ADP][Pi] was 59% of that found in larger infants (P less than 0.05). During reflex-induced isometric contractions in VLBW infants, [PCr]/([PCr]+[Pi]) declined by 24% and [ATP]/[ADP][Pi] declined by 35% (P less than 0.05 vs. rest). In all conditions, muscle pH remained 7.1. Overall, the differences in skeletal muscle energy state during rest and the corresponding changes in concentration of high-energy phosphates during mild exercise suggest a very limited energy reserve in the hypotonic muscle of VLBW infants.
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PMID:Muscle phosphorus energy state in very-low-birth-weight infants: effect of exercise. 155 Feb 22

A six-year-old boy presented with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination revealed mildly coarse facies, failure to thrive, generalized hypotonia with muscle wasting, and optic atrophy; there was no organomegaly. The family history suggested an X-linked recessive inheritance. The electroencephalogram, electroretinogram, evoked potentials, and computed axial tomography of the brain were abnormal. Urine oligosaccharide chromatography, urine amino acids and organic acids, and results of leukocyte and fibroblast lysosomal-enzyme assays for the known storage diseases were normal; however, conjunctival and renal biopsy specimens contained enlarged lysosomes on electron microscopy. The patient had progressive neurologic deterioration and died of renal failure at eight years of age. A compound identified as glutamyl ribose-5-phosphate was purified from the brain (0.96 mumol per gram, wet weight) and kidney (0.60 mumol per gram, wet weight). This compound is the linkage group in ADP-ribosylation of proteins, an important regulatory process in gene expression and DNA repair. We believe this new disorder represents a glycoproteinosis that results in the cytoplasmic storage of glutamyl ribose-5-phosphate.
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PMID:Progressive neurologic deterioration and renal failure due to storage of glutamyl ribose-5-phosphate. 673 1

Two new familial cases of 2-ketoglutarate dehydrogenase (2-KGD) deficiency are reported: a girl who died at 10 years and a boy, still alive at 4 years, born to consanguineous parents. The cases developed progressively severe encephalopathy with axial hypotonia, psychotic behaviour, pyramidal symptoms and failure to thrive. Both children exhibited permanent lactic acidosis with acute episodes during emotional stress and various infections, associated with elevated lactate/pyruvate (L/P) ratio and slightly decreased ketone body ratio in plasma. In fibroblasts, the L/P ratio was greatly increased in the boy. No respiratory chain complex deficiency could be demonstrated in cultured fibroblasts or in mitochondria isolated from a muscle biopsy performed on the boy. In muscle isolated mitochondria, a progressive decrease of the rate of glutamate oxidation was observed after ADP addition; the rate of 2-ketoglutarate oxidation was low in the absence of ADP and did not increase after ADP addition. 2-KGD deficiency was demonstrated in fibroblasts from both children and in the boy's muscle and myoblasts. The 2-KGD complex is composed of three separate enzymes: E1, E2 and E3. We could demonstrate in our patient that the E1 and E3 subunits were normal, suggesting that the E2 component could be responsible for the defect.
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PMID:2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary hyperlactataemia: report of a new case. 829 96

The F(o)F(1)-ATPase, a multisubunit protein complex of the inner mitochondrial membrane, produces most of the ATP in mammalian cells. Mitochondrial diseases as a result of a dysfunction of ATPase can be caused by mutations in mitochondrial DNA-encoded ATPase subunit a or rarely by an ATPase defect of nuclear origin. Here we present a detailed functional and immunochemical analysis of a new case of selective and generalized ATPase deficiency found in an Austrian patient. The defect manifested with developmental delay, muscle hypotonia, failure to thrive, ptosis, and varying lactic acidemia (up to 12 mmol/L) beginning from the neonatal period. A low-degree dilated cardiomyopathy of the left ventricle developed between the age of 1 and 2 y. A >90% decrease in oligomycin-sensitive ATPase activity and an 86% decrease in the content of the ATPase complex was found in muscle mitochondria. It was associated with a significant decrease of ADP-stimulated respiration of succinate (1.5-fold) and respiratory control with ADP (1.7-fold) in permeabilized muscle fibers, and with a slight decrease of the respiratory chain complex I and compensatory increase in the content of complexes III and IV. The same ATPase deficiency without an increase in respiratory chain complexes was found in fibroblasts, suggesting a generalized defect with tissue-specific manifestation. Absence of any mutations in mitochondrial ATP6 and ATP8 genes indicates a nuclear origin of the defect.
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PMID:Reduced respiratory control with ADP and changed pattern of respiratory chain enzymes as a result of selective deficiency of the mitochondrial ATP synthase. 1515 67

Succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP. It is a mitochondrial matrix enzyme and at least the ADP-forming enzyme is part of the Krebs cycle. The substrate specificity is determined by the beta subunit of succinate-CoA ligase, which is encoded by either SUCLA2 or SUCLG2. In patients with severe hypotonia, deafness and Leigh-like syndrome, mutations have been found in SUCLA2. Mutations have also been reported in SUCLG1, which encodes the alpha subunit found in both enzymes, in patients with severe infantile acidosis and lactic aciduria. Elevated methylmalonate and methylcitrate and severe mtDNA depletion were found in both disorders. The mtDNA depletion may be explained by the interaction of succinate-CoA ligase with nucleoside diphosphate kinase, which is involved in mitochondrial nucleotide metabolism.
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PMID:Disorders caused by deficiency of succinate-CoA ligase. 1839 45