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)

Three children displaying hypotonia, cardiac involvement and defects of the mitochondrial respiratory chain complexes are reported. The first case showed severe neonatal hypotonia, failure to thrive, hepatomegaly, dilation of the right cardiac cavities, profound lactic acidosis and amino aciduria. The boy died at the age of 7 weeks. In the second case hypotonia, severe cardiomyopathy, cyclic neutropenia, lactic acidosis and 3-methylglutaconic aciduria occurred. The boy died at the age of 27 months. The third case presented at the age of 16 months as an acute hypokinetic hypertrophic cardiomyopathy with transient hypotonia and mild lactic acidosis. Spontaneous clinical remission occurred. In all cases muscle biopsy was performed. Morphological studies failed to show ragged-red fibers but there was lipid storage myopathy and decreased cytochrome c oxidase activity. Biochemical studies confirmed the cytochrome c oxidase deficiency in muscle in all cases. It was associated with complex I III deficiency in case 1 and with severe deficits of all respiratory chain complexes in case 2. Post-mortem studies in case 1 indicated that complex IV was reduced in the liver but not in the heart and quantitative analysis of mtDNA revealed a depletion in muscle. Cases 1 and 2 shared some clinical features with fatal infantile myopathy associated with cytochrome c oxidase deficiency, while case 3 displayed a very unusual clinical presentation. The histochemical enzyme reaction of cytochrome c oxidase is useful for the diagnosis of mitochondrial myopathy because ragged-red fibers may be lacking. Finally, biochemical measurement of the different mitochondrial respiratory chain complexes is required because multiple defects are frequent and occasionally related to mtDNA depletion.
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PMID:Defects of the mitochondrial respiratory chain complexes in three pediatric cases with hypotonia and cardiac involvement. 132 Jun 61

A female child suffering from intrauterine growth retardation was born by caesarean section at 32 weeks. In the immediate newborn period there was a metabolic acidosis but this resolved. Hypotonia, muscular weakness and poor respiratory effort were evident and the child died at 6 days of age. A previous male sibling had died at 3 months of age after similar symptoms with seizures and a dysmyelination disorder. Post-mortem examination of both children showed damage to the basal ganglia. Defects in the activities of the pyruvate dehydrogenase complex, cytochrome oxidase and succinate cytochrome c reductase were found in cultured skin fibroblasts. Similar defects were found in isolated muscle mitochondria but not in isolated liver mitochondria from the patient. Immunoblotting for cytochrome oxidase showed that the multienzyme complex was not assembled in muscle and skin fibroblast mitochondria, but was assembled in liver mitochondria. Similar results were obtained in cultured skin fibroblast mitochondria for complex I of the mitochondrial respiratory chain. This is the first occasion that multiple defects have been demonstrated both in tissue and in culture skin fibroblasts in mitochondrial respiratory chain complexes.
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PMID:Fatal combined defects in mitochondrial multienzyme complexes in two siblings. 132 97

A newborn male with mitochondrial complex I deficiency suffered from neonatal epileptic seizures, which later developed into infantile spasms. The infant was blind due to aplasia of the retinal vessels and hypoplasia of the optic nerve. There was congenital lactic acidosis, which persisted in later life. The boy was microcephalic and retarded. Muscular hypotonia later shifted to spasticity. Succinic acid was increased in urine. We assume that the aplasia of the retinal vessels is due to damage of the retinal ganglion cells caused by the mitochondrial disease in the first 3 to 4 months of pregnancy.
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PMID:Aplasia of the retinal vessels combined with optic nerve hypoplasia, neonatal epileptic seizures, and lactic acidosis due to mitochondrial complex I deficiency. 139 14

Leigh's disease is one of the mitochondrial encephalomyopathies. This article presents a 7-month-old baby boy who had been well-being since birth until 6 months of age when episodic downward gaze of both eyes with limitation of horizontal eye movement were noted. This episode of cranial nerve palsies lasted about 4-5 days and subsided spontaneously. The second attack was noted one month later, to be associated with hypotonia and truncal ataxia. Episodic hyperventilation with resultant gasping and myoclonus was noted at the third attack but spontaneous respiration resumed soon with persistent ophthalmoplegia and truncal ataxia. Lumbar puncture, brain MRI, amino acid assay and cardiac echo all showed negative finding. The oral glucose lactate stimulation test revealed an elevation of lactic acid, brain stem evoked potential indicated bilateral obscure 4th and 5th waves, and muscle biopsy showed ragged red fibres with aggregation of structurally abnormal mitochondria noted under electron microscope. Coenzyme Q, thiamine and carnitine had been given before biochemical study; however, the neurological symptoms did not show any improvement. Biochemical study finally revealed normal respiratory chain enzymes including NADH-coenzyme Q reductase, succinate coenzyme Q reductase and cytochrome c oxidase while other enzymes were technically unavailable for study. Unfortunately the patient died at 18-month-old due to respiratory failure.
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PMID:Mitochondrial encephalomyopathy presenting with clinical Leigh's disease: report of a case. 184 64

We describe a girl with mitochondrial myopathy, who presented with general muscle weakness, muscle hypotonia and motor retardation. The level of blood lactate and pyruvate was consistently increased. Enzymatic studies showed impairment of NADH-dehydrogenase activity (complex I of the respiratory chain) in skeletal muscle. Electron-microscopy of a muscle biopsy showed abnormalities of a mitochondrial myopathy. The girl, now aged 30 months, has been treated with riboflavine (vitamin B2) since the age of 14 months, and lactate and pyruvate levels have decreased to normal. The patient still shows mild muscle hypotonia and weakness, but good motor progress and normal cognitive development.
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PMID:A mitochondrial myopathy in an infant with lactic acidosis. 236 46

Two siblings with infantile lactic acidosis and mitochondrial myopathy are described. The first child, a girl, died at 5 months of age from severe lactic acidosis after about 3 weeks of progressive muscular hypotonia. The younger brother had congenital lactic acidosis but no other symptoms until 6 months of age when progressive muscle weakness appeared. Treatment with dichloroacetate lowered the serum lactic acid level but did not affect his clinical condition. At 13 months of age, cardiomyopathy was diagnosed and he died at the age of 29 months of circulatory failure. Both children had mitochondrial myopathy. Postmortem examination of the boy revealed marked morphologic changes of the mitochondria in both skeletal muscle and the myocardium; biochemical investigation of skeletal muscle mitochondria demonstrated deficiencies in both complex I (NADH ferricyanide reductase) and complex IV (cytochrome c oxidase). The disease in these siblings differs in several respects from previously reported patients with mitochondrial myopathy and cytochrome c oxidase deficiency.
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PMID:Mitochondrial myopathy and cardiomyopathy in siblings. 274 28

Measurement of pyruvate and lactate produced from glucose by confluent skin fibroblast cultures from 95 patients with lactic acidemia revealed 10 in whom the lactate/pyruvate ratio (L/P) was increased (L/P = 57 to 232) compared with that observed in control cell lines (L/P = 18 to 35). Mitochondria prepared from these cells revealed two types of respiratory chain defect. In four patients the deficient activity was present in NADH-coenzyme Q reductase (14% to 21% of controls), and in six the deficiency was in cytochrome c oxidase (21% to 28% of controls). The four patients with NADH-coQ reductase deficiency presented early with lactic acidosis, respiratory failure, anorexia, and hypotonia; all four died within 7 months. The group with cytochrome oxidase deficiency had a somewhat later (18 months to 2 years of age) presentation with milder lactic acidemia, but also with hypotonia and anorexia. They had delayed development, beginning to walk and talk at 18 to 24 months, and then slowly regressed. Although an investigation of central nervous system disorders in this latter group has not been possible, the clinical progression fits into the broad category of Leigh disease. We conclude that in these two groups respiratory chain defects can be detected and localized by the use of skin fibroblast cultures.
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PMID:Clinical presentation of mitochondrial respiratory chain defects in NADH-coenzyme Q reductase and cytochrome oxidase: clues to pathogenesis of Leigh disease. 302 93

A mitochondrial defect was investigated in an infant with fatal congenital lactic acidosis (3-14 mM), high lactate-to-pyruvate ratio, hypotonia, and cardiomyopathy. His sister had died with a similar disorder. Resting oxygen consumption was 150% of controls. Pathological findings included increased numbers of skeletal muscle mitochondria (many with proliferated, concentric cristae), cardiomegaly, fatty infiltration of the viscera, and spongy encephalopathy. Mitochondria from liver and muscle biopsies oxidized NADH-linked substrates at rates 20-50% of controls, whereas succinate oxidation by muscle mitochondria was increased. Mitochondrial NADH dehydrogenase activity (complex I, assayed as rotenone-sensitive NADH oxidase, NADH-duroquinone reductase, and NADH-cytochrome c reductase) was 0-10% of controls, and NADH-ferricyanide reductase activity was 25-50% of controls in the mitochondria and in skin fibroblasts. Activities of other electron transport complexes and related enzymes were normal. Familial deficiency of a component of mitochondrial NADH dehydrogenase (complex I) proximal to the rotenone-sensitive site thus accounts for this disorder.
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PMID:Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport. Fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy. 311 Feb 16

In a 4.5-month-old boy presenting with marked muscular hypotonia in the neonatal period, hepatomegaly, cardiac hypertrophy, recurrent hypoglycemia, metabolic acidosis, and secondary carnitine deficiency, there was a considerable urinary excretion of 3-methylglutaconic and 3-methylglutaric acid. Estimation of 3-methylglutaconyl-CoA hydratase, 3-hydroxy-3-methylglutaryl-CoA lyase and initial enzymatic steps of cholesterol biosynthesis in cultured fibroblasts and in different tissues postmortem revealed no enzyme deficiency. Analyses of the respiratory chain in postmortem tissues demonstrated severe impairment of complex I (NADH ubiquinone oxidoreductase) and complex IV (cytochrome c oxidase) activities in skeletal muscle and reduced complex IV activity in heart.
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PMID:Multiple respiratory chain abnormalities associated with hypertrophic cardiomyopathy and 3-methylglutaconic aciduria. 769 3

A 4 1/2-month-old girl suffered from psychomotor retardation, generalized hypotonia, poor feeding, hyperreflexia, nystagmus, optical atrophy and choreoathetosis from the age of 3 months. Her blood lactate level was elevated to 40 mg/dL. Magnetic resonance imaging of her brain showed low T1 and high T2 signal intensities in the bilateral putamen, thalamus, red nuclei, substantia nigra, superior and inferior colliculi, cerebral peduncles and periaqueductal lesions. Muscle histochemistry and electron microscopic examinations were all normal except for variation in fiber size showing a myopathic change. An assay of muscle mitochondrial respiratory enzyme activities revealed a deficiency of NADH-coenzyme Q reductase. Molecular analysis did not reveal the putative T to G transversion at the nucleotide 8,993 of mitochondrial DNA in muscle biopsies. Leigh's disease was indicated by the clinical and radiologic manifestations. The patient died at 10 months of age from pneumonia and respiratory failure. There have been only sporadic reports of patients with Leigh's disease in Taiwan, and, to our knowledge, this is the first documented case of a Taiwanese patient with mitochondrial NADH-coenzyme Q reductase deficiency.
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PMID:Mitochondrial NADH-coenzyme Q reductase deficiency in Leigh's disease. 893 3


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