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 newborn infants, male (A) and female (B), with lethal hyperammonaemia are described in the same family. In both, symptoms started on the second day of life. Lethargy and hypotonia were the most prominent initial findings and were followed by convulsions and coma. In both, blood ammonia levels rose to 570 mumol/u (795 microgram/100 ml) a few hours before death, which occurred on the third and fourth day of life respectively. Assay of liver urea cycle enzymes in baby B showed a complete absence of mitochondrial carbamyl phosphate synthetase activity.
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PMID:Neonatal hyperammonaemia with complete absence of liver carbamyl phosphate synthetase activity. 20 10

Most inborn errors of intermediary metabolism presenting in the neonatal period fall schematically into three clinical categories: (1) those which lead to a neurological distress 'intoxication type' with a symptom-free interval, vomiting, comas, hypertonia, abnormal movements and frequent humoral disturbances (organic acidaemias, congenital urea cycle defects); (2) those which lead to a neurological distress 'energy deficiency' type. Frequent symptoms in this group include hyperlactacidaemia, severe hypotonia, cardiomyopathy, failure to thrive and malformations (congenital lactic acidaemias, fatty acid oxidation defects, peroxysomal disorders); (3) those which present evidence of liver dysfunction and hepatomegaly (glycogenesis, neoglucogenesis defects, galactosaemia, fructosaemia, tyrosinaemia type I). According to these three major clinical presentations and according to the proper use of few screening tests (blood gases, glucose, ammonia, lactic acid, electrolytes, acetest), we propose a method of diagnosis which groups these children into five schematical syndromes: type I MSUD; type II organic acidaemias; type III; congenital lactic acidosis; type IVa, urea cycle defects; type IVb, non-ketotic hyperglycinaemia, sulfite oxidase deficiency, peroxisomal disorders; type V liver dysfunctions. Once the above classification has been made, sophisticated and specific investigations can be planned (amino acid chromatography, organic acid chromatography, enzymatic studies, etc).
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PMID:Clinical approach to inherited metabolic disorders in neonates. 226 19

In order to evaluate significance and frequency of valproic acid (VPA)-induced hyperammonemia we measured venous serum ammonia, SGOT, G-GT, platelets and antiepileptic drug levels in three groups of subjects: 1.) 30 pediatric patients treated with VPA, alone or in combination 2.) 30 healthy age and sex matched subjects 3.) 30 pediatric unselected patients treated with various antiepileptic drugs except VPA. In the VPA group serum ammonia was significantly (p less than 0.01) higher than in controls and in the group 3. Patients on VPA-polytherapy had significantly higher serum ammonia values than patients on VPA-monotherapy (p less than 0.01). Hyperammonemia was found in 8 (27%) VPA-treated patients. A syndrome consisting of lethargy, stupor, hypotonia and increased seizure activity developed in 3 patients on VPA-therapy of whom two showed hyperammonemia. After discontinuing VPA this syndrome disappeared in all three cases. There was no direct correlation between VPA and ammonia levels. The etiology of hyperammonemia in VPA treated patients is not yet fully explained. It may be related to the fatal VPA induced hepatic failure reported in the literature. Some risk factors which may facilitate hepatic injury during VPA therapy (young age, co-medication, polytherapy, infectious disease, protein overload, low caloric intake) are discussed and some practical consequences are indicated.
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PMID:[Hyperammonemia in valproate therapy in children and adolescents]. 308 61

Non-ketotic hyperglycinemia is one of inborn metabolic errors that manifest by epileptic seizures of difficult control from the first days of life in hypotonic newborn children. The lack of enzyme that catalyzes the conversion of glycine to hydroxymethyltetrahydrofolic acid, carbon dioxide and ammonia, in liver and brain, results in increased concentration of glycine in blood. It is reported in this study a case of non-ketotic hyperglycinemia diagnosed in neonatal period and characterized by hypotonia and non-controlled multiple seizures. The clinical and electroencephalographic findings, treatment as well as anatomopathologic study are discussed.
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PMID:[Non-ketotic hyperglycinemia. Study of a case]. 360 38

A symptomatic elevation in plasma ammonium concentration, termed hyperammonemia, is associated with numerous congenital and acquired conditions (Table 11). In some cases, such as urea cycle disorders, ammonia is the principal toxin. In other instances, such as portal systemic encephalopathy, it is but one of a number of metabolic disturbances, However, in either case hyperammonemic episodes should be treated aggressively to prevent coma, subsequent brain damage, or death. This involves restricting protein intake, providing adequate calories, and giving agents that remove accumulated nitrogen. Long-term therapy relies on diagnosing the specific disease rate. This rarely requires invasive procedures such as liver biopsy. In most cases measurement of plasma amino acids and urinary organic acids will identify the defect. Treatment involving restriction of nitrogen intake, vitamin supplementation, or stimulation of alternative pathways of waste nitrogen excretion can then be instituted. Early therapy, especially in patients with neonatal-onset hyperammonemia, is imperative to avoid severe brain damage. On this basis, the plasma ammonium level should be determined in virtually every newborn with lethargy, hypotonia, poor feeding, seizures, and/or respiratory distress of unclear origin (Table 12).
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PMID:Hyperammonemia. 651 17

Shortly after birth, a newborn girl developed anorexia, hypotonia, apneic attacks and seizures. After 61 h the child died in coma. Biochemically, a highly elevated blood ammonia level was found together with an increased plasma level of the amino acids mainly involved in ammonia detoxication. Enzyme studies in post-mortem liver tissue material revealed a deficiency of carbamoyl-phosphate synthetase (0.9% of the mean value in controls) in combination with an intermediate activity of L-ornithine: 2-oxoglutarate aminotransferase (40% of the mean value in controls).
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PMID:A lethal neonatal variant of carbamoyl-phosphate synthetase deficiency in combination with an intermediate activity of L-ornithine: 2-oxoglutarate amino-transferase. 685 Dec 28

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 4.5-year-old boy with chronic progressive encephalopathy is described. The clinical presentation initially included seizures and hypotonia which later evolved into severe extrapyramidal disease and dementia. The gas chromatography/mass spectrometry (GC/MS) analysis of urine indicated that alpha-ketoglutarate was increased 210 times and aconitic acid 80 times. No disturbance of acid/base balance, lactic acid or ammonia metabolism accompanied this clinical picture. The fibroblasts contained 29% of normal alpha-ketoglutarate dehydrogenase activity, while the activity of another mitochondrial marker enzyme, glutamate dehydrogenase, was normal. The neuroimaging studies revealed bilateral striatal necrosis. The clinical and biochemical findings were almost identical to two previously reported patients. Experience with this patient emphasizes the need for detailed organic acid biochemical investigation in any progressive encephalopathy and that extrapyramidal tract signs should evoke the possibility of alpha-ketoglutaric aciduria, among other 'neurologic organic acidemias'.
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PMID:A new patient with alpha-ketoglutaric aciduria and progressive extrapyramidal tract disease. 772 79

Citrullinemia, a rare inborn error of metabolism, is characterized by a deficiency of argininosuccinic acid synthetase that results in large increases in plasma ammonia, citrulline, and glutamine, with normal acid-base balance. The neurologic symptoms vary from poor feeding, vomiting, and irritability to hypotonia, apnea, and death. The most common pathologic findings at autopsy are cerebral edema and focal neuronal necrosis. We describe a case of fulminant citrullinemia in an infant in whom the major pathologic findings included diffuse cerebral edema and a lack of overt metabolic derangement characteristic of neonates with a urea cycle defect. Our case differs from the classic presentation of citrullinemia in that subarachnoid hemorrhage was identified early in the clinical course. We report the first observation of subarachnoid hemorrhage in an infant with a urea cycle defect.
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PMID:Perinatal pathology casebook. 886 47

A 3-day-old infant presented with anorexia, irritability, hypotonia, and seizures. Blood ammonia was 2115 micromol/L and amino and organic acid analyses were consistent with ornithine transcarbamylase deficiency. Liver biopsy confirmed only 1% enzyme activity. The patient was treated with hemodialysis. An electroencephalogram (EEG) revealed multifocal independent spike-and-sharp-wave discharges. After initial stabilization he was placed on a low-protein diet with citrulline and phenylbutyrate. Conjugating agents (arginine, sodium benzoate, and sodium phenylacetate) have been added during periods of metabolic decompensation. Although developmentally delayed, the patient has shown signs of clinical improvement and EEG activity has likewise improved with only mild background slowing and no evidence of epileptogenic activity at 4 years of age. A second infant presented at 3 days of age with a similar history, blood ammonia of 1382 micromol/L, and metabolic studies indicative of ornithine transcarbamylase deficiency. EEG showed multifocal independent ictal and interictal discharges. Electrographic abnormalities persisted despite lowering of blood ammonia with hemodialysis and conjugating agents. The patient continued to decline clinically and died on the 7th hospital day. EEG changes parallel the clinical course of ornithine transcarbamylase deficiency and may serve as an objective marker of the effectiveness of therapeutic interventions.
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PMID:Electroencephalographic findings in ornithine transcarbamylase deficiency. 1045 65


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