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)

Two children are described who suffered from episodes of metabolic acidosis and progressive mental and motor deterioration. The patients showed periodic elevation of blood lactate, pyruvate and alanine, which was accompanied by vomiting, hypotonia or convulsions. The concentrations of lactate and pyruvate in cerebrospinal fluid were found to be increased. Liver biopsies revealed a decrease in pyruvate carboxylase activity and normal pyruvate decarboxylase activity. No inhibitor of TPP-ATP phosphoryl transferase was detected in urine from the patients. These findings suggest that congenital lactic acidosis due to pyruvate carboxylase deficiency is probably a different disease entity from Leigh's encephalomyelopathy. A possible mechanism of brain damage caused by a defect in pyruvate carboxylase is postulated.
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PMID:Congenital lactic acidosis due to pyruvate carboxylase deficiency: absence of an inhibitor of TPP-ATP phosphoryl transferase. 20 66

The purpose of the study was differential diagnosis of lactic acidosis in 44 children aged from 2 weeks to 4 years. In all of them the lactate level in repeated determinations exceeded 27 mg/100 ml. From the point of view of clinical manifestations the children were divided into three groups: 26 with hepatomegaly and hypoglycaemia (I), 6 with ataxia and retardation of somatic development (II), 12 with mental retardation and muscular hypotonia (III). Together with basic biochemical studies other tests were done, if necessary, including glucose and alanine loading, lactate determination in cerebrospinal fluid, analysis of urinary organic acids by the GC-MS method, morphological examinations of muscle biopsy material, enzymatic determinations in liver biopsy material. In group I glycogenosis was suspected and its type was finally established after biochemical and enzymatic tests (types I, Ib, III, VI, VIa, XI). In one case fructose-1,6-diphosphatase deficiency was suspected. In group II the clinical manifestations resembled Leigh's syndrome. The tests demonstrated an inhibition of glucose formation from alanine, and lactate level in the cerebrospinal fluid was evidently raised above that in the serum. Gasometric index showed the presence of respiratory alkalosis with metabolic compensation rather than primary lactate acidosis. In group III, with considerable clinical variety of signs, in only nine out of 12 children the cause of lactate acidosis could have been established (pathological changes of mitochondria in 4 cases, secondary increase of lactate without pathogenetic importance in 4, and 3-hydroxy-3-methylglutaric acidosis in 1 case. In conclusion it is thought that this combination of diagnostic methods is useful in differential diagnosis of congenital lactate acidosis in children.
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PMID:Congenital lactic acidosis in children--differential diagnosis in 44 cases. 184 18

Pyruvate carboxylase deficiency results in congenital lactic acidosis. We report the significant finding in a child with infantile spasms controlled with adrenocorticotrophin hormone (ACTH) but who then developed severe lactic acidosis; pyruvate carboxylase deficiency was subsequently diagnosed. Blood lactate, pyruvate, and alanine levels were elevated, as well as cerebrospinal fluid alanine. Plasma alanine concentration was doubled by ACTH therapy. Fibroblasts contained extremely low pyruvate carboxylase activity. The patient died at 12 weeks of age after recurrent episodes of profound acidosis. At autopsy, the brain manifested cystic degeneration and demyelination. Pyruvate carboxylase deficiency is associated with neonatal onset of acidosis, delayed development, seizures, hypotonia, recurrent profound acidosis, and early death. The dramatic rise in plasma alanine content coincident with ACTH therapy suggest that ACTH played a role in precipitating the catastrophic metabolic acidosis.
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PMID:Pyruvate carboxylase deficiency: acute exacerbation after ACTH treatment of infantile spasms. 255 27

A female infant presented with signs of general muscle hypotonia and increasing hypertrophy of the heart muscle. There was a constant lactic acidosis worsened after glucose intake. Serum lactate levels were increased up to 6.7 mmol/l. Serum alanine levels reached maximum concentrations of 2,800 mumol/l. The patient died after sudden cardiac arrest at 22 months of age. Histology of the heart showed the pattern of foamy myocardial transformation with accumulation of mitochondria and an increased glycogen content. Biochemical analysis of the skeletal muscle and the heart demonstrated signs of a disturbed respiratory chain. The content of cytochrome aa3 protein was decreased in skeletal muscle and heart mitochondria. It is suggested that respiratory chain defects may be the cause of foamy myocardial transformation of the heart.
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PMID:Foamy myocardial transformation in a child with a disturbed respiratory chain. 282 64

A new patient with Leigh's syndrome (subacute necrotizing encephalomyelopathy due to pyruvate dehydrogenase complex deficiency) is presented. A Turkish boy of consanguinously married healthy parents developed progressive muscle weakness since infancy. At the age of 3 years he was unable to sit, stand or walk. Clinical examination showed general muscle weakness, hypotonia, muscle hypotrophy, bilateral ptosis, partial bilateral external ophthalmoplegia, nystagmus, intention tremor and hypoactive tendon reflexes. The EEG showed diffuse slowing, the cerebral CT scan disclosed mild hydrocephalus e vacuo. Motor nerve conduction velocity was slightly decreased, the EMG revealed signs of neuropathy. In the biopsied muscle only a mild hypotrophy of type 2 fibres was found, no abnormal mitochondria could be detected. The sural nerve was slightly abnormal: loss of large myelinated axons, loss of unmyelinated nerves. CSF protein was elevated to 80 mg/dl, protein electrophoresis revealed the pattern of markedly impaired blood-CSF barrier. Serum lactate and pyruvate were permanently elevated. In the urine the excretion of alanine was raised. The clinical state deteriorated during intercurrent infections; somnolence, vomiting and Cheyne-Stoke's respiration occurred. At the age of 3 1/2 years the child died of pneumonia. In the liver tissue a decreased activity of the pyruvate dehydrogenase complex was found. Neuropathological examination of the brain demonstrated wide-spread changes of Leigh's spongiform encephalopathy. Several enzyme deficiencies have hitherto been associated with Leigh's syndrome: This patients confirms earlier findings that a subgroup of Leigh's syndrome is caused by pyruvate dehydrogenase complex deficiency.
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PMID:[Leigh's subacute necrotizing encephalomyelopathy due to decreased activity of the pyruvate dehydrogenase complex]. 312 26

A male infant had severe muscular hypotonia from birth. Recurrent vomiting with dehydration and severe metabolic acidosis complicated the course. Elevated lactate (up to 12.3 mmol/l; n less than 2), pyruvate (0.4 mmol/l; n less than 0.05) and alanine levels were found in serum with an abnormal lactate/pyruvate ratio (greater than 30; n less than 15). In urine the concentrations of lactate, pyruvate, alanine and of several intermediates of the citric acid cycle were increased. In muscle, numerous disseminated "ragged red fibres" were found by light microscopy; muscle fibres were found to contain subsarcolemmal aggregates of mitochondria, lipid droplets and glycogen by electromicroscopical methods. Moreover, mitochondria with a typical circular arrangement of cristae were noticed. In liver homogenates normal activities of pyruvate carboxylase and pyruvate dehydrogenase complex were found; in liver mitochondria also succinate-cytochrome-c-oxidoreductase activity was normal. However, in muscle no succinate-cytochrome-c-oxidoreductase activity was detectable. The patient became increasingly lethargic and died because of sepsis at 5 months of age.
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PMID:Mitochondrial myopathy with lactic acidosis and deficient activity of muscle succinate cytochrome-c-oxidoreductase. 609 51

Bejar et al. described increased concentrations of valine, leucine and isoleucine in the plasma of 2 patients with cerebral gigantism (Sotos-syndrome). We have recently investigated a group of 14 children with Sotos-syndrome. The data of the plasma amino-acid determinations were compared with those of aged-matched healthy controls, 9 children with benign muscular hypotonia, 10 children with Down's syndrome and finally with those of 13 children with familial tall stature. The mean concentration of serine, glutamic acid, valine, isoleucine, leucine and phenylalanine was lower in the patients with Sotos-syndrome when compared to the healthy control group. However, all patients with benign muscular hypotonia and Down's syndrome showed increased concentrations of proline, glycine, alanine, ornithine and lysine in the plasma whereas the mean values of the children with familial tall stature differed only slightly from those of the controls. The levels of the plasma-aminoacids in patients with Sotos-syndrome were only slightly different from those in patients with muscular hypotonia, but generally lower than in tall children. We conclude that the determination of plasma-aminoacids is of no value in the diagnosis of Sotos-syndrome.
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PMID:[Amino acids in plasma of patients with cerebral gigantism (Sotos syndrome) (author's transl)]. 645 99

A 4-year-old patient is described with hyperphenylalaninemia, severe retardation in development, severe muscular hypotonia of the trunk and hypertonia of the extremities, convulsions, and frequent episodes of hyperthermia without infections. Urinary excretion of neopterin, biopterin, pterin, isoxanthopterin, dopamine, and serotonin was very low, although the relative proportions of pterins were normal. In lumbar cerebrospinal fluid, homovanillic acid, 5-hydroxyindoleacetic acid, neopterin and biopterin were low. Oral administration of L-erythro tetrahydrobiopterin normalized the elevated serum phenylalanine within 4 h, serum tyrosine was increased briefly and serum alanine and glutamic acid for a longer time. Urinary dopamine and serotonin excretion were also increased. Administration of an equivalent dose of D-erythro tetrahydroneopterin was ineffective and demonstrated that this compound is not a cofactor in vivo and cannot be transformed into an active cofactor. GTP cyclohydrolase I activity was not detectable in liver biopsies from the patient. The presence of an endogenous inhibitor in the patient's liver was excluded. This is the first case of a new variant of hyperphenylalaninemia in which the formation of dihydroneopterin triphosphate and its pterin metabolites in liver is markedly diminished. Normal activities of xanthine oxidase and sulfite oxidase were apparent since uric acid levels were normal and no increase in hypoxanthine, xanthine, and S-sulfocysteine concentrations could be observed in urine. It is concluded that the molybdenum cofactor of these enzymes may not be derived from dihydroneopterin triphosphate in man. Also, since no gross abnormalities in the patient's immune system could be found, it seems unlikely that dihydroneopterin triphosphate metabolites, such as neopterin, participate actively in immunological processes, as postulated by others. See Note added in proof.
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PMID:GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia. 673 69

The clinical and biochemical findings in a patient with the inherited disease so called hyperammonemia type II are presented. The patient was a male who had the first abnormal symptoms of tremors and continuous crying at 35 hours of age and exhibited a rapid clinical course dying 62 hours after birth. Rejection of food, respiratory problems, hypotonia and tonic-clonic convulsions were other outstanding clinical symptoms observed. Withdrawal of the feedings and initiation of a perfusion did not improve the clinical picture. Biochemical studies in samples of blood, urine and CSF revealed the presence of high concentrations of ammonia, alanine, glutamine and orotic acid. Final diagnosis was achieved when post mortem liver ornithine transcarbamylase activity was found to be lower than 6% with respect to that of adequate controls. Carbamyl phosphate synthetase, another urea cycle enzyme measured, was within normal limits of activity.
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PMID:[Neonatal hyperammonemia due to ornithine transcarbamylase deficiency (author's transl)]. 711 19

A 23-month-old boy with progressive muscular hypotonia and mental and motor deterioration was described. Four days after the admission he had a respiratory arrest and required the care in a respirator thereafter. Laboratory examinations showed metabolic acidosis and high levels of pyruvate, lactate and alanine in blood and cerebrospinal fluid. Oral administration of thiamine-HCl and lipoic acid was noneffective and he died 7 months after the admission. Autopsy findings were compatible with subacute necrotizing encephalomyelopathy (Leigh's disease). The activity of pyruvate decarboxylase in autopsy samples was not detectable and that in fibroblasts was 9% of that in control cell lines. The present study confirmed that pyruvate decarboxylase deficiency is one of the causes of Leigh's disease.
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PMID:Pyruvate decarboxylase deficiency in a patient with Leigh's encephalomyelopathy. 712 39


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