Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMINO ACIDURIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed1984

Simpler liquid-chromatographic screening for organic acid disorders.

We describe an isocratic cation-exchange chromatographic technique, with ultraviolet detection, for determination of urinary organic acids. The method is useful for screening urines from neonates and infants suspected of having an organic aciduria, prior to confirmatory analysis by gas chromatography-mass spectrometry. Advantages of this technique over conventional gas chromatography include ease of sample preparation and the simultaneous detection of volatile fatty acids; limitations include its lack of an identification system like that of mass spectrometry, the presence of nonultraviolet-absorbing fatty acids, and the relatively long retention times of phenolic compounds. Chromatograms for patients with methylmalonic aciduria, propionic aciduria, isovaleric aciduria, beta-ketothiolase deficiency, lactic aciduria, and glutaric aciduria type II are compared with those for a normal infant.

Adult↗
PubMed1997

A review of phylogenetic and metabolic relationships between the acylamino acids, N-acetyl-L-aspartic acid and N-acetyl-L-histidine, in the vertebrate nervous system.

N-Acetyl-L-histidine (NAH) and N-acetyl-L-aspartic acid (NAA) are major constituents of vertebrate brain and eye with distinct phylogenetic distributions. They are characterized by high tissue concentrations, high tissue/extracellular fluid gradients, and a continuous regulated efflux into the extracellular fluid. As a result of parallel investigations over the past three decades, evidence has accumulated that suggests that the metabolism of NAA in the CNS of both homeothermic and poikilothermic vertebrates and the metabolism of NAH in the CNS of poikilothermic vertebrates are related. Tissue distribution and concentrations are similar, as well as timing of appearance during embryological development and their synthetic and degradative biochemistry. Both amino acids appear to be involved in a rapid tissue-to-fluid-space cycling phenomenon across a membrane. Evidence accumulating for each amino acid suggests a dynamic and important role in the CNS and the eye of vertebrates. A genetic disease in humans, Canavan's disease, is associated with NAA aciduria and aspartoacylase deficiency with concomitant accumulation of NAA and a spongy degeneration of the brain. In this article, evidence linking NAA and NAH metabolism is reviewed, and the hypothesis that NAA and NAH complement each other and are metabolic analogues involved with membrane transport is developed. Their enzyme systems also appear to exhibit plasticity in relation to osmoregulatory forces on an evolutionary time scale, with an apparent interface at the fish-tetrapod boundary.

Animals↗
PubMed2003

Diffusion-weighted imaging in the assessment of neurological damage in patients with methylmalonic aciduria.

Diffusion-weighted magnetic resonance imaging (DW-MRI) of the brain was performed in two patients with methylmalonic aciduria who presented signs and symptoms of neurological involvement without metabolic decompensation. Patient 1 presented acute metabolic stroke and patient 2 presented subacute encephalopathy. Brain DW-MRI confirmed very recent damage in patient 1, while the absence of brain lesions on brain DW-MRI indicates the development of more chronic damage in patient 2. Brain DW-MRI represents an additional and complementary tool in the assessment of brain damage in methylmalonic aciduria patients who develop neurological syndrome.

Adolescent↗
PubMed1984

Occurrences of methylmalonic aciduria and Hartnup disorder in the same family.

Methylmalonic aciduria and Hartnup disorder are two rare autosomal recessively inherited metabolic disorders. We have described the coexistence of these disorders within the same pedigree in two unrelated families. This association was not found in 57 other families surveyed because of a proband known to have either methylmalonic aciduria or Hartnup disorder.

Adult↗
PubMed2002

3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings.

Type III 3-methylglutaconic aciduria (MGA) (MIM 258501) consists of early bilateral optic atrophy, later development of spasticity, extrapyramidal dysfunction and occasionally cognitive deficits, and urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. The presence of the disorder in an Iraqi-Jewish genetic isolate led to mapping of the OPA3 gene to chromosome 19q13.2-q13.3, followed by isolation of the gene itself. OPA3 consists of two exons and codes for a peptide of 179 amino acids. Iraqi-Jewish patients with type III MGA are homozygous for a splice site founder mutation in OPA3 (IVS1-1G>C) which abolishes mRNA expression in fibroblasts. Here we report a novel mutation in OPA3 (320-337del) in a Kurdish-Turkish patient with optic atrophy and 3-methylglutaconic and 3-methylglutaric aciduria, previously carrying the diagnosis of type IV MGA. We conclude that type III MGA occurs in patients of non-Iraqi-Jewish ancestry, and should be considered in patients with type IV MGA that have optic atrophy and ataxia.

Adolescent↗
PubMed1990

[Biochemical diagnosis of rare hereditary metabolic disorders. Experiences from a patient sample of the Innsbruck University Pediatric Clinic 1984-1987].

The diagnosis of inherited metabolic diseases requires an intensive cooperation between the clinician, the clinical chemist and the biochemist to select patients for an adequate screening program, to avoid unnecessary expensive investigations and to achieve a final molecular diagnosis. Often a cooperation with specialized laboratories even in different countries is necessary. 29 patients with an inherited metabolic disorder have been evaluated at the Children's Hospital, University of Innsbruck, between 1984 and 1987. Seven patients with a disturbance in carbohydrate metabolism incl. pyruvate oxidation, nine with a defect in amino or organic acid metabolism, eleven patients with a lysosomal storage disorder, one patient with steroid-sulfatase deficiency and one with M. Wilson have been found. In nine of these 29 patients an organic aciduria was detected, four of them had lactic aciduria due to a mitochondrial defect of the oxidative energy metabolism. 21 children corresponded to a well-known classic phenotype, eight represented very rare or unique, not previously described clinical forms of a disease. In one third of the cases a cooperation with a foreign institute was necessary. The presentation of the most important biochemical investigations in children with inherited metabolic defects should give a survey of the diagnosis of such patients at a pediatric centre and should furthermore stimulate the development of a common diagnostic procedure program and the cooperation and coordination of the laboratories involved in the diagnosis of inherited metabolic disorders in Austria.

Amino Acid Metabolism, Inborn Errors↗
PubMed1995

Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients.

Holocarboxylase synthetase (HCS) deficiency is an inherited disease of biotin metabolism characterized by a unique pattern of organic aciduria, metabolic acidosis, and skin lesions. By analysis of five patients in four unrelated families, two mutations were identified: a transition from T to C which causes an amino-acid substitution of proline for leucine at position 237 (L237P) and a single deletion of guanine (delG1067) followed by premature termination. One patient was homozygous for the L237P mutation, three patients in two families were compound heterozygotes of the missense and deletion alleles, and the other patient was heterozygous for the L237P mutation. Inheritance was successfully demonstrated in all of the patients' families by a modified PCR followed by restriction enzyme digestion. The two mutations accounted for seven of eight mutant alleles, while neither mutation was detected in 108 normal healthy Japanese children (216 alleles). Transient expression in cultured fibroblasts from a patient showed that the L237P mutation was responsible for decreased HCS activity. These results suggest that the L237P and delG1067 mutations are frequent disease-causing mutations in Japanese patients with HCS deficiency. This PCR-based technique may therefore be useful for detecting mutations among Japanese patients.

Amino Acid Sequence↗
PubMed1984

Urea cycle function in the dog with emphasis on the role of arginine.

English Pointer puppies were used in experiments designed to assess urea cycle function. A preliminary assay revealed a dietary arginine (Arg) requirement of 0.40% for maximal weight gain of puppies fed a chemically defined L-amino acid diet. Subsequent studies showed that consumption of an Arg-free diet resulted in growth failure, emetic episodes, mild hyperammonemia, decreased plasma Arg and urea, and orotic aciduria. Oral administration of ornithine (Orn), equimolar to 0.40% Arg, failed to correct these Arg deficiency symptoms. Consumption of an equimolar concentration of citrulline (Cit), on the other hand, resulted in near normal weight gains, but blood and urine metabolite levels still did not parallel those of dogs fed Arg. Plasma glucose concentration was unaffected by dietary treatment. Older dogs (20 weeks of age) performed no better than younger dogs (7 weeks of age) when fed an Arg-free diet. In a serial bleeding study, plasma ammonia increased after ingestion of an Arg-free diet, reached a peak during emesis and declined immediately thereafter. In contrast, plasma ammonia of dogs fed an Arg-adequate diet remained relatively constant. It was apparent that in terms of meaningful Arg replacement value, Orn had minimal activity. Cit could replace Arg for growth, but was not as efficient as Arg for urea cycle function.

Age Factors↗
PubMed1981

[Lysinuric protein intolerance: a severe hyperammonemia secondary to l-arginine deficiency (author's transl)]].

Lysinuric protein intolerance is an autosomal recessive disease, due to a defect in intestinal, renal and hepatic dibasic amino acid transport. Two new cases in the same family are reported. The disease appears progressively during the first months of life with failure to thrive, anorexia, vomiting, diarrhea, hepatosplenomegaly, muscular weakness, osteoporosis, anemia, leukothrombocytopenia, hyperammonemia and orotic aciduria after a high-protein intake. Hyperdibasicamino-aciduria was associated with subnormal plasma concentrations of the same aminoacids. Oral l-arginine, l-ornithine, l-lysine, and lysyl-glycine loads confirmed the diagnosis. The supplementation of the diet with l-citrulline resulted in normal levels of blood ammonia. However, hepatosplenomegaly, muscular weakness, osteoporosis remained unchanged and growth was not improved. These may be due to lysine deficiency.

Amino Acid Metabolism, Inborn Errors↗
PubMed1986

Conditional deficiencies of ornithine or arginine.

Relative deficiencies of ornithine or arginine occur in the presence of excessive ammonia, excessive lysine, growth, pregnancy, trauma, or protein deficiency and malnutrition. Ammonia excess may occur in the presence of a normal liver when amino acid mixtures lacking ornithine, arginine, or citrulline are infused; when specific amino acids such as glycine are injected; when ammonium salts, urea, or urease are injected; or when the gastrointestinal tract contains an excess of protein, urea, or NH4+, as occurs after a gastrointestinal hemorrhage. In these states, ornithine is often rate-limiting for urea cycle function. Ornithine is also rate-limiting when ammonia excess occurs in the presence of hepatic failure. In three of the inherited urea cycle disorders, ornithine insufficiency and ammonia excess also occur. These disorders are citrullinemia, argininosuccinic aciduria, and argininemia. In the presence of excessive lysine the availability of arginine is reduced and the formation of ornithine is decreased in the liver; urea synthesis is reduced, but orotic acid synthesis is increased, and orotic aciduria results as carbamyl phosphate is directed toward the pyrimidine pathway. Hereditary lysinuric protein intolerance results in ornithine depletion, hyperammonemia, and orotic acid uria. Optimal growth in several species of animals requires 0.4-1.0% arginine in the diet. Diets deficient in arginine are associated with poor wound healing as well as stunted growth. The measurement of orotic acid excretion has been a convenient indicator of insufficiency of ornithine or arginine during growth or pregnancy in animals and should prove useful in assessing the requirement for arginine after trauma. Normal human pregnancy is associated with low-grade orotic aciduria. Protein deficiency and malnutrition increase the vulnerability of the animal or child to ammonia toxicity. This is presumably due to insufficient ornithine for normal urea cycle responsiveness.

Amino Acids↗
PubMed1992

Molecular cloning of human mevalonate kinase and identification of a missense mutation in the genetic disease mevalonic aciduria.

Mevalonic aciduria is the first proposed inherited disorder of the cholesterol/isoprene biosynthetic pathway in humans, and it is presumed to be caused by a mutation in the gene coding for mevalonate kinase. To elucidate the molecular basis of this inherited disorder, a 2.0-kilobase human mevalonate kinase cDNA clone was isolated and sequenced. The 1188-base pair open reading frame coded for a 396-amino acid polypeptide with a deduced M(r) of 42,450. The predicted protein sequence displayed similarity to those of galactokinase and the yeast RAR1 protein, indicating that they may belong to a common gene family. Southern hybridization studies demonstrated that the mevalonate kinase gene is located on human chromosome 12 and is a single copy gene. No major rearrangements were detected in the mevalonic aciduria subject. The relative size (2 kilobases) and amounts of human mevalonate kinase mRNA were not changed in mevalonic aciduria fibroblasts. Approximately half of the mevalonic aciduria cDNA clones encoding mevalonate kinase contained a single base substitution (A to C) in the coding region at nucleotide 902 that changed an asparagine residue to a threonine residue. The presence of this missense mutation was confirmed by polymerase chain reaction amplification and allele-specific hybridization of the genomic DNAs from the proband and the proband's father and brother. Similar analysis failed to detect this mutation in the proband's mother, seven normal subjects, or four additional mevalonic aciduria subjects, indicating that the mutation does not represent a common gene polymorphism. Functional analysis of the defect by transient expression confirmed that the mutation produced an enzyme with diminished activity. Our data suggest that the index case is a compound heterozygote for a mutation in the mevalonate kinase gene.

Amino Acid Sequence↗
PubMedDate not supplied

[Glutaric aciduria type 1: an example of the importance of early detection of so-called cerebral organic aciduria].

Glutaric aciduria type 1 (GA 1) is a preventable cause of acute brain damage in early childhood, leading to a severe dystonic-dyskinetic disorder. Typically between 6 and 18 months of age, a non-specific illness such as respiratory or gastrointestinal infection or immunization leads to encephalopathic crisis, usually resulting in degeneration of the putamen and caudate. GA 1 is an autosomal recessive disease of catabolism of amino acids lysine, hydroxylysine and tryptophane leading to accumulation of glutaric acid, 3-hydroxyglutaric acid and glutaconic acid. Recognition of this biochemical disorder before the brain has been injured is essential to the outcome. Diagnosis depends upon the recognition of relatively non-specific physical findings such as hypotonia, tremor, irritability and macrocephaly, and on urinary organic acids analysis. The diagnosis may also be suggested by characteristic findings of neuroimaging. Specific management includes pharmacological doses of 1-carnitine and dietary protein restriction. Metabolic decompensation must be treated vigorously to avoid permanent brain damage. With this case report the authors want to contribute to the early recognition of GA1, to the prevention of the related brain damage, and to increase awareness of the existence of so-called cerebral organic acidurias.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

Plasma concentrations and renal clearance of orotic acid in argininosuccinic acid synthetase deficiency.

Argininosuccinic acid synthetase deficiency (ASD) is a rare disorder of urea cycle metabolism, with pronounced citrullinemia and orotic aciduria being characteristic biochemical features. To further investigate the role of plasma orotic acid and its possible use for monitoring the metabolic status in ASD, we determined plasma orotic acid, amino acid, and ammonium levels in plasma samples collected over a period of 3 years from a patient who is now 8 years of age. Orotic acid plasma concentrations varied widely from less than 1 micromol/l to more than 60 micromol/l. The renal clearance of orotic acid was eightfold the glomerular filtration rate, thus supporting an active mechanism underlying the excretion of this pyrimidine. Data obtained during a metabolic crisis yielded a statistically significant linear correlation of orotic acid plasma levels with those of glutamine and ammonium, which are generally accepted for assessment of the successful treatment of this disorder. Our data revealed no advantage of plasma orotic acid concentrations over the established amino acids (glutamine and arginine) and ammonium for determining acute treatment responses. Since several effects of high levels of orotic acid have been described in mammals, further research is necessary to assess a possible contribution of orotic acid to the pathogenesis of ASD and the use of plasma orotic acid levels in the long-term monitoring of these patients.

Amino Acids↗