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 685 records · Page 38Linked to original sources
PubMed2003

A knock-out mouse model for methylmalonic aciduria resulting in neonatal lethality.

Methylmalonic aciduria is a human autosomal recessive disorder of organic acid metabolism resulting from a functional defect in the activity of the enzyme methylmalonyl-CoA mutase. Based upon the homology of the human mutase locus with the mouse locus, we have chosen to disrupt the mouse mutase locus within the critical CoA binding domain using gene-targeting techniques to create a mouse model of methylmalonic aciduria. The phenotype of homozygous knock-out mice (mut-/-) is one of early neonatal lethality. Mice appear phenotypically normal at birth and are indistinguishable from littermates. By 15 h of age, they develop reduced movement and suckle less. This is followed by the development of abnormal breathing, and all of the mice with a null phenotype die by 24 h of age. Urinary levels of methylmalonic and methylcitric acids are grossly increased. Measurement of acylcarnitines in blood shows elevation of propionylcarnitine with no change in the levels of acetylcarnitine and free carnitine. Incorporation of [14C]propionate in primary fibroblast cultures from mut-/- mice is reduced to approximately 6% of normal level, whereas there is no detectable synthesis of mut mRNA in the liver. This is the first mouse model that recapitulates the key phenotypic features of mut0 methylmalonic aciduria.

Alkyl and Aryl Transferases↗
PubMed2004

Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria.

d-2-hydroxyglutaric aciduria is a neurometabolic disorder with both a mild and a severe phenotype and with unknown etiology. Recently, a novel enzyme, d-2-hydroxyglutarate dehydrogenase, which converts d-2-hydroxyglutarate into 2-ketoglutarate, and its gene were identified. In the genes of two unrelated patients affected with d-2-hydroxyglutaric aciduria, we identified disease-causing mutations. One patient was homozygous for a missense mutation (c.1331T-->C; p.Val444Ala). The other patient was compound heterozygous for a missense mutation (c.440T-->G; p.Ile147Ser) and a splice-site mutation (IVS1-23A-->G) that resulted in a null allele. Overexpression studies in HEK-293 cells of proteins containing the missense mutations showed a marked reduction of d-2-hydroxyglutarate dehydrogenase activity, proving that mutations in the d-2-hydroxyglutarate dehydrogenase gene cause d-2-hydroxyglutaric aciduria.

Alcohol Oxidoreductases↗
PubMed1988

[Protein intolerance with lysinuria. Value of orotic aciduria in adjusting treatment with citrulline].

A new case of lysinuric protein intolerance is described in a 14 year-old Maghrebian child who presented with growth failure, vertebral osteoporosis, aversion to proteins and digital hippocratism, rarely described in this disease. Orotic aciduria was studied after a protein load with and without citrulline supplement and during the course of a 11 month-treatment. There was a clear relationship between orotic aciduria, protein intake and citrulline supplementation. Orotic aciduria appears to be very useful to adjust the treatment.

Adolescent↗
PubMed2006

Evidence that oxidative stress is increased in plasma from patients with maple syrup urine disease.

Maple syrup urine disease (MSUD) or branched-chain alpha-keto aciduria (BCKA) is an inherited disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKAD) activity. The blockage of this pathway leads to tissue accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine and their respective keto-acids. The clinical features presented by MSUD patients include ketoacidosis, convulsions, coma, psychomotor delay and mental retardation. The mechanism of brain damage in this disease is still poorly understood. However, an increase in lipid peroxidation in vitro in cerebral cortex of young rats as well as a decrease in the antioxidant defenses has been previously observed. In the present work we evaluated different oxidative stress parameters, named reactive species of thiobarbituric acid (TBARS), total antioxidant reactivity (TAR) and total antioxidant status (TAS) in plasma of MSUD patients in order to evaluate whether oxidative stress is involved in this disorder. We verified a marked increase of plasma TBARS measurements, which is indicative of increased lipid peroxidation, as well as a decrease on plasma TAR reflecting a deficient capacity to efficiently modulate the damage associated with an increased production of reactive species. In contrast, TAS was not changed indicating that the total content of antioxidants in plasma of patients affected by MSUD was not altered. These results suggest that free radical generation is elicited in MSUD and is possibly involved in the pathophysiology of the tissue damage found in this disorder.

Antioxidants↗
PubMedDate not supplied

Acrodermatitis acidemica secondary to malnutrition in glutaric aciduria type I.

We encountered a patient with glutaric aciduria type I (GA-I) associated with skin lesions resembling acrodermatitis enteropathica (AE). This child was being fed with a low-protein diet when the skin disorder developed. A deficiency in plasma levels of essential amino acids, particularly isoleucine, and zinc was confirmed. Supplementation of a high-caloric, protein-rich diet together with zinc, selenium and vitamins led to a prompt improvement of the skin lesions. We assume that in our patient the skin lesions were the result of malnutrition, rather than being primarily associated with the underlying metabolic disease. To our knowledge, no other report is so far available concerning GA-I complicated by skin eruptions.

Acrodermatitis↗
PubMed1991

[Macrocephaly as the initial manifestation of glutaryl-CoA-dehydrogenase deficiency (glutaric aciduria type I)].

Glutaric aciduria type I is due to an impaired glutaryl-CoA-dehydrogenase with an increased urinary excretion of glutaric and 3-OH glutaric acid. Typically, the clinical course until the sixth month or even 3rd year of life is symptom free, and only later an encephalopathic crisis develops. The only symptom of our 4 patients was macrocephaly (head circumference greater than 97. percentile) in early infancy. 3 of them suffered from an encephalopathic crisis at 8 months to 3 years of age; during that time they lost already established abilities as sitting, walking and speaking, and developed choereoathetotic movements. One child aged 15 months was normal beside it's macrocephalus. All children were treated with a diet low in lysine (80 mg/kg BW/day), tryptophane (21 mg/kg BW/day), and by supplementation of L-carnitine (200 mg/kg BW/day) and riboflavine (200 mg/day) and the motorically disturbed children received Lioresal 1 mg/kg BW/day. The effect of this treatment cannot be evaluated so far, but there is evidence that the dietetic therapy together with carnitine supplementation may prevent further deterioration in affected, or an encephalopathic crisis in unaffected patients. Therefore we suggest to investigate organic acids in urine in every child or infant with macrocephalus to exclude glutaric aciduria type I.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

Neonatal screening for glutaric aciduria type I: strategies to proceed.

Acute encephalopathic crisis in glutaric aciduria type I results in an unfavourable disease course and poor outcome, dominated by dystonia, feeding problems, seizures and reduced life expectancy. A conditio sine qua non for the prevention of irreversible brain damage is timely diagnosis and start of therapy, i.e. before the onset of neurological disease. As there are no specific clinical signs or symptoms that allow a reliable detection of these patients before the manifestation of encephalopathic crises, neonatal screening programmes for glutaric aciduria type I have been established in some countries using analysis of glutarylcarnitine in dried blood spots by tandem mass spectrometry. This article summarizes recent strategies, pitfalls and shortcomings of mass screening for glutaric aciduria type I, focusing on the relevant risk of missing patients with a mild biochemical phenotype (i.e. low excretors). Furthermore, it evaluates a binary strategy--using glutarylcarnitine as primary variable and glutarylcarnitine/acylcarnitine ratios as secondary variable--to improve the diagnostic sensitivity and specificity of neonatal screening for glutaric aciduria type I. An optimization of diagnostic as well as therapeutic procedures must be achieved before screening for glutaric aciduria type I can be regarded as reliable and beneficial for all patients.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

[Cutaneous lesions and blood count changes in a 9-month old girl with glutaric aciduria type I].

Non-specific cutaneous lesions are common in patients suffering from acute myeloid leukemia (AML). Leukemic skin infiltrates are present in about 30% of cases of monoblastic or myelomonocytic leukemia. The appearance of specific skin lesions can precede bone marrow involvement. We report the case of a 9-month-old girl with acute myelogenous leukemia (FAB M5) and glutaric aciduria type I which initially presented with cutaneous lesions, anemia and leukopenia.

Amino Acid Metabolism, Inborn Errors↗
PubMed2002

Dietary arginine slightly and variably affects tissue polyamine levels in male swiss albino mice.

Many key metabolic and physiologic functions involve arginine and arginine-derived metabolites. Requirements for arginine, a "conditionally essential" amino acid for most mammalian species, are met in variable proportions by dietary intake and endogenous synthesis, the latter being sufficient to fulfill arginine needs in adult humans and mice under nonpathologic conditions. However, dietary arginine restriction causes orotic aciduria and abnormal function of the urea cycle. Furthermore, the importance of dietary arginine in the maintenance of homeostasis of arginine-derived metabolites in the body has not yet been analyzed in detail. We therefore examined whether the deprivation or supplementation of dietary arginine affects tissue and circulating levels of arginine-derived polyamines. We pair-fed male Swiss albino mice (30 g) for 15 or 30 d synthetic diets containing 0, 1.12 or 2.24 g/100 g L-arginine. Tissue and blood levels of the main free polyamines, putrescine, spermidine and spermine, were measured by HPLC. In general, neither the deprivation nor the supplementation of arginine dramatically affected the levels of any of the polyamines analyzed. Variations were organ, time and polyamine specific, and most differences were in the levels of putrescine at 15 d and of spermidine at 30 d. Thus, in contrast to effects on urea cycle function, dietary arginine does not appear to be essential for the maintenance of the homeostasis of free polyamine levels in adult mice, emphasizing the importance of endogenous arginine synthesis in preserving the polyamine body pool.

Animals↗
PubMed1988

The effects of fetal energy depletion on amniotic fluid concentrations of amino acids, organic acids and related metabolites.

Concentrations of amino and organic acids, phosphate, sulphate, gluconic acid and gluconolactone were measured in amniotic fluid samples which contained either normal or raised hypoxanthine concentrations. In this way, the effect of mild fetal ATP depletion could be determined. The effects of this mild asphyxia were to raise concentrations of phenylalanine, tyrosine, lysine, glycine, phosphate, sulphate, gluconic acid and glucono-1,5-lactone. However, concentrations of a variety of other metabolites were unchanged; thus no diagnostic confusion should arise with organic acidurias in mild asphyxia in contrast to the biochemical mimickry produced by severe asphyxia. Since clinically normal parturition can produce changes in amniotic fluid, urine from newborn or cord blood may not reflect the metabolic balance in utero.

Adenosine Triphosphate↗
PubMed1989

Orotic aciduria due to arginine deprivation: changes in the levels of carbamoyl phosphate and of other urea cycle intermediates in mouse liver.

The orotic aciduria induced in mammals by arginine deprivation is believed to result from accumulation of carbamoyl phosphate in liver, but this accumulation has never been demonstrated in vivo during arginine deprivation. There has been disagreement even on the basal levels of carbamoyl phosphate. In this report we show, using an improved assay, that the hepatic level of carbamoyl phosphate is very low (less than 1.3 nmol/g) in the fasted mouse or after a meal containing a mixture of amino acids including arginine, and that it increases dramatically (up to 180 nmol/g liver) after a meal without arginine. We estimated a fast turnover for carbamoyl phosphate, and we found a marked correlation between liver carbamoyl phosphate and urinary orotate, and also between urinary orotate and intake of an arginine-free diet. These results support the hypothesis that accumulation of carbamoyl phosphate in liver mitochondria, its efflux from this organelle and its utilization by the cytosolic pyrimidine pathway cause the orotic aciduria of arginine deprivation. We assayed liver acetylglutamate (the activator of carbamoyl phosphate synthesis) and several intermediates of the urea cycle and found that low levels of ornithine partly explain the accumulation of carbamoyl phosphate during arginine deprivation. However, acetylglutamate and citrulline were increased, and the potential significance of these changes is discussed.

Animals↗
PubMed1981

Formiminoglutamic aciduria in a slightly retarded boy with chronic obstructive lung disease.

A 2-year-old boy excreted massive amounts of formiminoglutamic acid in urine. The substance was identified as authentic formiminoglutamic acid by two-dimensional thin-layer chromatography, column chromatography and enzymatic determination. After alkaline hydrolysis the substance was converted to glutamic acid. Serum amino acid concentrations were normal. The patient had normal serum and erythrocyte folate levels. The red blood cell picture was normal. The leukocytes showed slight hypersegmentation. From the age of 3 months he exhibited recurrent otitis media and severe pulmonary infections. He had a peculiar narrow-headed look and marked universal hypotonia. The mental development was slightly retarded. Glutamate formiminotransferase deficiency is postulated. The findings lend support to the theory of glutamate formiminotransferase deficiency being a rather benign disorder of metabolism.

Child, Preschool↗
PubMed1995

Use of human somatotrophin in the treatment of a patient with methylmalonic aciduria.

Growth hormone (GH) insufficiency was demonstrated in a patient with methylmalonic aciduria. GH administration at 14-21 U/m2 per week accelerated linear growth, stimulated lipolysis, and produced clinical improvement and reduced urinary methylmalonate excretion. The clinical and metabolic benefits were lost as the dose of GH was increased to 28 U/m2 per week. CONCLUSION. The use of GH in other patients with methylmalonic aciduria (and other disorders of intermediary metabolism demonstrating similar clinical and metabolic features) warrants further study.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Quantification of carnitine and specific acylcarnitines by high-performance liquid chromatography: application to normal human urine and urine from patients with methylmalonic aciduria, isovaleric acidemia or medium-chain acyl-CoA dehydrogenase deficiency.

This paper describes the development of a high-performance liquid chromatographic method for the quantitation of free carnitine, total carnitine, acetylcarnitine, propionylcarnitine, isovalerylcarnitine, hexanoylcarnitine and octanoylcarnitine in human urine. Carnitine and acylcarnitines were isolated from 10 or 25 microliters of urine using 0.5-ml columns of silica gel, derivatized with 4'-bromophenacyl trifluoromethanesulfonate and separated by high-performance liquid chromatography. Using 4-(N,N-dimethyl-N-ethylammonio)-3-hydroxybutanoate ("e-carnitine") as the internal standard, standard curves (10-300 nmol/ml) were generated. Carnitine and acylcarnitines were quantified (when they were present) in normal human urine and the urine of patients diagnosed with one of three different disorders of organic acid metabolism: methylmalonic aciduria, isovaleric aciduria, isovaleric acidemia, and medium-chain acyl-CoA dehydrogenase deficiency.

Acetophenones↗
PubMed1976

Beta-methylcrotonic aciduria associated with lactic acidosis.

A patient is described in whom lactic acidosis of very severe degree was found to coincide with the presence of beta-methylcrotonic acid and rho-hydroxyphenyllactic acid in urine in large amounts, while beta-hydroxyisovaleric acid was found to be a relatively minor excretion product. Beta-methylcrotonic acid is demonstrated, for the first time, to be present in blood and CSF. These findings are discussed in relation to the patients previously reported to have beta-methylcrotonylglycinuria and raise the possibility that our patient's organic aciduria may be secondary to acquired disease rather than to an inborn error of metabolism.

Amino Acids↗
PubMed1979

Congenital defect in intracellular cobalamin metabolism resulting in homocysteinuria and methylmalonic aciduria. I. Case report and histopathology.

The case is described of an infant who suffered from progressive, severe dystrophy, hemolytic and megaloblastic anemia, hematuria, proteinuria and slight uremia. He died at 4 months of age following two acute episodes of heart failure. Abnormally increased excretion of methylmalonate and homocystine was detected by our screening program for metabolic disorders. Amino acid analyses showed that the plasma and urine levels of methionine were very low whereas those of cystathionine were raised. Vitamin B12 deficiency, malabsorption or abnormal cobalamin transport were excluded by a normal serum total cobalamin and normal transcobalamins. These findings suggested a congenital error of cobalamin metabolism. Treatment with vitamin B12 resulted in a biochemical though not a clinical response. Postmortem examination revealed severe vascular lesions with changes in the kidney characteristic of thrombotic microangiopathy supporting a diagnosis of hemolytic-uremic syndrome. It is assumed that the elevated plasma homocysteine induced the vascular lesions by causing detachment of endothelium.

Blood Vessels↗