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 793 records · Page 44Linked to original sources
PubMed1983

Metabolic response to carnitine in methylmalonic aciduria. An effective strategy for elimination of propionyl groups.

Patients with methylmalonic aciduria have an excessive intramitochondrial accumulation of acylcoenzyme A compounds that may reduce the availability of free coenzyme A (CoA) for normal metabolic requirements, producing profound metabolic disturbances. Giving carnitine to a patient with methylmalonic aciduria produced an increase in hippurate excretion (an index of intramitochondrial adenosine triphosphate (ATP) and CoA availability), a large increase in short chain urinary acylcarnitines, and a reduction in excretion of methylmalonate and methylcitrate. These acylcarnitines were shown by fast atom bombardment and B/E linked scan mass spectrometry to be propionylcarnitine and acetylcarnitine. Carnitine acts by removing (detoxifying) propionyl groups, thereby releasing CoA and restoring ATP biosynthesis and concentrations towards normal. L-carnitine may play a central role in maintenance of mitochondrial and cellular homoeostasis in methylmalonic aciduria and propionic acidaemia. These principles may provide an approach to the treatment of this and other disorders, inherited and acquired, in which accumulation of acyl CoA metabolites results in sequestration of free CoA, thereby perturbing metabolic homoeostasis.

Acetylcarnitine↗
PubMed1975

[Chronic hyperammonemia with orotic aciduria: evidence of pyrimidine pathway stimulation (author's transl)].

We have investigated a 3 year old girl with mental and physical retardation, chronic hyperammonemia and orotic aciduria. Plsma glutamine, alanine and proline concentrations were high. Alanine was present in her urine. She excreted only half the urea of control subjects on a similar protein intake. Raising protein intake induced NH4 intoxication with convulsion. Orotic aciduria was present (max: 693 mg/day) and was related to NH4 levels. Red blood cell orotate phosphoribosyl transferase and orotidine decarboxylase activieé were normal, eliminating congenital orotic aciduria, with induction of activity seen on repeated assay during protein load (form 1.37 to 7.5 nmole/109 RBC/hr). Blood ammonia rose with ornithine load, while ornithine levels were twice that of controls. Citrulline was normally metabolized. Although lacking liver assay, we have provided evidence of partial ornithine carbamyl transferase deficiency. The importance of orotic aciduria for ammonia detoxication in partial OCT deficiency is shown, and its possible effect on liver lipoprotein synthesis discussed. Our investigation also confirmed that OCT activity is not present in normal leukocytes rendering them useless for OCT deficiency diagnosis.

Alanine↗
PubMed2002

A novel stop codon mutation (X465Y) in the argininosuccinate lyase gene in a patient with argininosuccinic aciduria.

Argininosuccinate lyase (ASL) deficiency (McKusick 207900) is a rare autosomal recessive disorder affecting the urea cycle. The cardinal symptom in the neonatal form is progressive hyperammonemia, which is often life-threatening. However, clinical symptoms in the late onset form are quite heterogeneous. As well as measurement of ASL activity, analysis of the ASL gene is necessary to clarify the genetic basis of various phenotypes. We report a patient with late onset argininosuccinate lyase deficiency (ASLD) who had hepatomegaly and mildly increased level of ammonia. By mutation analysis of the mRNA and genomic DNA from the patient's leukocytes, we identified a novel missense mutation 1395G>C in the homozygous state, which results in the exchange of a stop codon to tyrosine at amino acid position 465 (X465Y). This unique mutation causes an elongation of fifty amino acids in the C-terminal region of the ASL protein, and is likely related to a milder phenotype compared with previously reported mutations. In addition, this is the first report on mutation analysis in a Japanese ASLD patient.

Amino Acid Sequence↗
PubMed2004

Pathomechanisms of neurodegeneration in glutaryl-CoA dehydrogenase deficiency.

Glutaryl-CoA dehydrogenase deficiency is an inherited organic aciduria with predominantly neurological presentation. Biochemically, it is characterized by an accumulation and enhanced urinary excretion of two key organic acids, glutaric acid and 3-hydroxyglutaric acid. If untreated, acute striatal degeneration is often precipitated by febrile illnesses during a vulnerable period of brain development in infancy or early childhood, resulting in a dystonic dyskinetic movement disorder. The mechanism underlying these acute encephalopathic crises has been partially elucidated using in vitro and in vivo models. 3-Hydroxyglutaric and glutaric acids share structural similarities with the main excitatory amino acid glutamate and are considered to play an important role in the pathophysiology of this disease. 3-Hydroxyglutaric acid induces excitotoxic cell damage specifically via activation of N-methyl-D-aspartate receptors. Furthermore, glutaric and 3-hydroxyglutaric acids indirectly modulate glutamatergic and GABAergic neurotransmission, resulting in an imbalance of excitatory and inhibitory neurotransmission. It also has been suggested that secondary amplification loops potentiate the neurotoxic properties of these organic acids. Probable mechanisms for this effect include cytokine-stimulated nitric oxide production, a decrease in energy metabolism, and reduction of cellular creatine phosphate levels. Finally, maturation-dependent changes in the expression of neuronal glutamate receptors may affect the vulnerability to 3-hydroxyglutaric and glutaric acid toxicity.

Amino Acid Metabolism, Inborn Errors↗
PubMed1978

3-methylglutaconic aciduria: report on a sibship with infantile progressive encephalopathy.

Choreoathetosis, spastic parapareses, dementia and optic atrophy were the main clinical features in a sibship with progressive encephalopathy of late onset. The urine contained constantly elevated amounts of 3-methylglutaric and 3-methylglutaconic acids. The identity of these metabolites was confirmed by synthesis and mass spectrometry. On leucine loading, the excretion of the metabolites was elevated.

Amino Acid Metabolism, Inborn Errors↗
PubMed2005

Creatine metabolism in combined methylmalonic aciduria and homocystinuria.

Methylation is an important aspect of many fundamental biological processes including creatine biosynthesis. We studied five patients with an inborn error of cobalamin metabolism to characterize the relation between homocysteine and creatine metabolism. Plasma guanidinoacetate concentrations were increased, 14.9 +/- 4.8 micromol/L (p < 0.0001), whereas plasma creatine concentrations were in the low reference range, 43.8 +/- 20.7 micromol/L (p = not significant). Individuals with combined methylmalonic aciduria and homocystinuria have a functional impairment of the creatine synthetic pathway probably secondary to a relative depletion of labile methyl groups. The neurotoxic effects of guanidinoacetate may be partly responsible for the observed neurological phenotype.

Adult↗
PubMedDate not supplied

Ocular findings in glutaric aciduria type 1.

PURPOSE: To determine the nature and course of ocular abnormalities in glutaric aciduria (acidemia) type 1 (GA1). METHODS: Fifteen children with GA1 have been studied in the Republic of Ireland. A retrospective review of the records of the 6 children who died during their illness and prospective clinical examination of 9 survivors were performed. RESULTS: Seven of the 15 children had abnormal eye findings. Ocular complications included intraretinal hemorrhages, cataract, gaze palsy, strabismus, ametropia, and pigmentary retinopathy. CONCLUSION: Ocular involvement is common in glutaric aciduria. Complete ophthalmologic evaluation is recommended in all patients suspected to have this rare disease. Intraretinal hemorrhages due to GA1 could be misinterpreted as resulting from child abuse, and it is important to include this disorder with the differential diagnosis of child abuse.

Amino Acid Metabolism, Inborn Errors↗
PubMed2003

Methylmalonic acid, a biochemical hallmark of methylmalonic acidurias but no inhibitor of mitochondrial respiratory chain.

Methylmalonic acidurias are biochemically characterized by an accumulation of methylmalonic acid and alternative metabolites. An impairment of energy metabolism plays a key role in the pathophysiology of this disease, resulting in neurodegeneration of the basal ganglia and renal failure. It has become the subject of intense debates whether methylmalonic acid is the major toxin, inhibiting respiratory chain complex II. To elucidate whether methylmalonic acid is a respiratory chain inhibitor, we used spectrophotometric analysis of complex II activity in submitochondrial particles from bovine heart, radiometric analysis of 14C-labeled substrates (pyruvate, malate, succinate), and analysis of ATP production in muscle from mice. Methylmalonic acid revealed no direct effects on the respiratory chain function, i.e. on single electron transferring complexes I-IV, ATPase, and mitochondrial transporters. However, we identified a variety of variables that must be carefully controlled to avoid an artificial inhibition of complex II activity. In summary, the study verifies our hypothesis that methylmalonic acid is not the major toxic metabolite in methylmalonic acidurias. Inhibition of respiratory chain and tricarboxylic acid cycle is most likely induced by synergistically acting alternative metabolites, in particular 2-methylcitric acid, malonic acid, and propionyl-CoA.

Acyl Coenzyme A↗
PubMed2003

Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid 5beta-reductase, in hepatitis and liver failure in infancy.

BACKGROUND: A substantial group of patients with cholestatic liver disease in infancy excrete, as the major urinary bile acids, the glycine and taurine conjugates of 7alpha-hydroxy-3-oxo-4-cholenoic acid and 7alpha,12alpha-dihydroxy-3-oxo-4-cholenoic acid. It has been proposed that some (but not all) of these have mutations in the gene encoding delta(4)-3-oxosteroid 5beta-reductase (SRD5B1; AKR1D1, OMIM 604741). AIMS: Our aim was to identify mutations in the SRD5B1 gene in patients in whom chenodeoxycholic acid and cholic acid were absent or present at low concentrations in plasma and urine, as these seemed strong candidates for genetic 5beta-reductase deficiency. PATIENTS AND SUBJECTS: We studied three patients with neonatal onset cholestatic liver disease and normal gamma-glutamyl transpeptidase in whom 3-oxo-delta(4) bile acids were the major bile acids in urine and plasma and saturated bile acids were at low concentration or undetectable. Any base changes detected in SRD5B1 were sought in the parents and siblings and in 50 ethnically matched control subjects. METHODS: DNA was extracted from blood and the nine exons of SRD5B1 were amplified and sequenced. Restriction enzymes were used to screen the DNA of parents, siblings, and controls. RESULTS: Mutations in the SRD5B1 gene were identified in all three children. Patient MS was homozygous for a missense mutation (662 C>T) causing a Pro198Leu amino acid substitution; patient BH was homozygous for a single base deletion (511 delT) causing a frame shift and a premature stop codon in exon 5; and patient RM was homozygous for a missense mutation (385 C>T) causing a Leu106Phe amino acid substitution. All had liver biopsies showing a giant cell hepatitis; in two, prominent extramedullary haemopoiesis was noted. MS was cured by treatment with chenodeoxycholic acid and cholic acid; BH showed initial improvement but then deteriorated and required liver transplantation; RM had advanced liver disease when treatment was started and also progressed to liver failure. CONCLUSIONS: Analysis of blood samples for SRD5B1 mutations can be used to diagnose genetic 5beta-reductase deficiency and distinguish these patients from those who have another cause of 3-oxo-delta(4) bile aciduria, for example, severe liver damage. Patients with genetic 5beta-reductase deficiency may respond well to treatment with chenodeoxycholic acid and cholic acid if liver disease is not too advanced.

Chenodeoxycholic Acid↗
PubMed1989

[Pernicious anemia with indicanuria].

A 67-year-old female was diagnosed as having classical pernicious anemia. Laboratory data included low serum vitamin B12 concentrations, abnormal deoxyuridine suppression test, methylmalonic aciduria, atrophic gastritis, positive anti-intrinsic factor antibody and Schilling test results typical of pernicious anemia. During hospitalization it was incidentally noted that her urine was green colored. Jaffe' reaction and Obermayer reaction for indicanuria were both positive. Dark purple crystalline material was obtained by centrifugation of her urine. The crystalline substance was soluble in methanol and its absorbance curve was identical to that of authentic indoxylsulphate potassium salt. Daily output of this substance was nearly 50 times normal. There was no increase in urinary excretion of monoamino-monocarboxyl amino acides. The exact reason for her indicanuria was not clear, although abnormal bacterial growth in the intestine remained as a possibility.

Aged↗
PubMed1981

The adult presenting idiopathic Fanconi syndrome.

The adult presenting Fanconi syndrome is a rare familial disorder. A 30-year follow-up of one of the original families in the literature is reported here. Two important points have emerged. Firstly, the inheritance in this family is dominant, not recessive as originally suggested, and there remains no good example in the literature of a recessive inheritance of this disorder. Second, in this family lactic aciduria and tubular proteinuria are probably the earliest manifestations of the disorder in childhood, with glycosuria and aminoaciduria developing in the second decade and osteomalacia from the start of the fourth decade. Glomerular function deteriorates slowly but is compatible with a normal lifespan.

Adult↗
PubMed1985

Glutaric aciduria type I misdiagnosed as Leigh's encephalopathy and cerebral palsy.

Two cases are reported of boys who suffer epileptic seizures only after playing video games. It is suggested that the amount of time the patient spends in front of the screen before the seizure is important, and also that video games trigger electrocortical activity far more efficiently than either television or intermittent photic stimulation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Methylmalonic aciduria (cblF): case report and response to therapy.

Methylmalonic acidemia can be secondary to a deficiency of methylmalonyl CoA mutase or to a defect of cobalamin metabolism that is classified by complementation group. We report on a new patient with cblF complementation group that is associated with an elevation of both methylmalonic acid and homocysteine, and her outcome in response to routine therapy and a dietary restriction.

Adolescent↗
PubMed1979

Argininosuccinic aciduria: prenatal studies in a family at risk.

We have monitored two successive pregnancies in a family which we found to be at risk for argininosuccinic aciduria. We measured argininosuccinic acid (ASA) concentrations in amniotic fluid and utilized an indirect assay of ASA lyase activity in cultured amniotic fluid cells. The assay procedure is based on the uptake of 14C from [14C]citrulline and of [3H]leucine into protein. ASA was easily measured in amniotic fluid from the first fetus at risk, whereas none was detectable in control fluids. Amniotic fluid cells cultured from this fetus had only 5.5% of control ASA lyase activity. The pregnancy was terminated, and hepatic ASA lyase activity in the fetus was shown to be about 1.3% of control values. In addition, eight fetal tissues were analyzed for ASA, and all had significant accumulation. ASA was not detected in amniotic fluid from the second fetus at risk, and ASA lyase activity in cultured cells was 80% of control activity. Enzymatic analysis of erythrocyte lysate confirmed the diagnosis of an unaffected child (ASA lyase = 46% of control) and indicated heterozygosity. Thus, we provide further evidence that argininosuccinic aciduria can be diagnosed successfully in utero by indirect assay of ASA lyase activity in cultured amniotic fluid cells. In addition, high amniotic fluid ASA concentrations provide strong adjunctive evidence for such a prenatal determination, and may prove to be sufficient for diagnosis.

Adult↗
PubMed1997

A two-base deletion in exon 6 of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene producing the skipping of exons 5 and 6 determines 3-hydroxy-3-methylglutaric aciduria.

A novel two-base deletion in the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene was found in a Spanish patient with homozygous 3-hydroxy-3-methylglutaric aciduria. Amplification by RT-PCR of the mRNAs showed that the gene was transcribed into three different mRNAs. One showed the complete deletion of exons 5 and 6 located between nucleotides 348 and 561 of the HL cDNA. The second transcript showed deletion of exon 6 only, and the third contained a two-base deletion CT in exon 6, corresponding to nucleotides 504 and 505 of the HL cDNA. These aberrant mRNAs are predicted to encode three abnormal HMG-CoA lyase proteins; the first (from skipped exons 5 and 6) lacks 71 amino acids, which represents 24% of the mature protein; the second, (from the skipping of exon 6, producing a frameshift) contains only 192 amino acids, the last 26 of which are missense amino acids preceding a stop codon; the third contains only 175 amino acids, the last 7 of which are missense. Northern blot analysis showed that the HL mRNA levels of the patient were 4% of the control. PCR quantitative analysis indicated that the mRNA lacking exons 5 and 6 was the most abundant, representing 88% of the total. The other two mRNAs represented 8% and 4%, respectively. In the genomic DNA only one CT deletion was found at positions +7 and +8 at beginning of exon 6. No mutations were observed in the splice donor, splice acceptor, or pyrimidine-rich sequences of the intronic regions flanking exons 5 and 6. All three aberrant mRNAs resulted only from the deletion of nucleotides CT. We suggest that this deletion may affect the interaction between the small nuclear ribonucleoproteins (snRNPs) and exon 6, and that, as a result, the abnormal splicing of the pre-mRNA produces two different aberrant transcripts.

Adolescent↗
PubMed1989

4-Hydroxybutyric aciduria: further clinical heterogeneity in a new case.

A 2.5-year-old girl presented with severely delayed speech development and mild motor retardation. Urinary organic acid analysis showed the presence of 4-hydroxybutyric acid and other metabolites consistent with the diagnosis 4-hydroxybutyric aciduria. Succinic semialdehyde dehydrogenase activity was absent in lymphocyte lysates. The clinical symptoms in this case were unusually mild compared to previously reported patients. No correlation was found between the mild symptoms and the levels of metabolite excretion or the residual succinic semialdehyde dehydrogenase activity in this patient compared to more severely affected cases.

Amino Acid Metabolism, Inborn Errors↗
PubMed1980

Diagnostic value of orotic acid excretion in heritable disorders of the urea cycle and in hyperammonemia due to organic acidurias.

Orotic acid excretion in urine in increased in ornithine transcarbamylase deficiency, citrullinemia and argininemia; it is barely increased in argininosuccinic aciduria and normal in carbamylphosphate synthetase deficiency and in hyperammonemia due to organic aciduria. The determination of orotic acid excretion is useful in differentiating the cases of hyperammonemia and reduces the need for enzymatic assays on tissue biopsies for decisions on therapy. The data indicate that orotic acid does not merely reflect ammonia concentration in plasma, but depends on carbamylphosphate concentration. Arginine could play a key role in the regulation of ammonia detoxication.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

[Abnormal antioxidant system in inborn errors of intermediary metabolism].

INTRODUCTION: Oxidative stress may be implied in the pathogenic mechanisms of inborn errors of intermediary metabolism (IEIM). OBJECTIVE: The evaluation of the antioxidant status in IEIM by the measurement of erythrocyte antioxidant enzyme activities, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase and catalase. PATIENTS AND METHODS: 34 patients with IEIM: 1) eleven with organic acidurias on protein restricted diet; 2) nine without special diet; 3) five patients with aminoacidopathies on protein restriction; 4) three patients with galactosemia and six with aminoacidopathies on protein free diet. Erythrocyte antioxidant enzymes were measured by spectrometric procedures adapted to the Cobas Fara II analyser. RESULTS: SOD activity was significantly higher in groups 2 and 4 (p= 0.009, p= 0.001, respectively), and significantly lower in group 3 (p= 0.001) compared with age matched controls. SOD activity was significantly higher in the patients with IEIM on protein free diet (groups 2 and 4) compared with those on protein restricted diet (groups 1 and 3; p= 0.002) or with controls (p= 0.003). GPx activity was found significantly lower in group 1 patients (p= 0.004), and higher in group 2 (p= 0.029) compared with controls. CONCLUSIONS: 35% of the patients with IEIM had SOD activity above the control range, most of them with organic acidurias or homocystinuria, suggesting an induction of enzyme protein synthesis owing to an excess of free radical generation. The lower activities observed in patients on natural protein restriction may likely be due to a deficient bioavailability of antioxidant cofactors.

Amino Acid Metabolism, Inborn Errors↗