1/11. 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.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
2/11. Type II citrullinemia in an elderly patient treated with living related partial liver transplantation.A 60-year-old woman was admitted to our hospital for repeated consciousness disturbance. blood examination showed hyperammonemia, and plasma amino acid analysis revealed a marked increase in the citrulline level. To establish a diagnosis, a percutaneous needle biopsy of the liver was performed. The determination of the urea cycle enzyme activities revealed a selective marked decrease in argininosuccinate synthetase activity, indicating the final diagnosis of type II citrullinemia. The mean survival period of this disease after the appearance of symptoms has been reported as 26.4 months, and most conservative treatments are not effective. We performed a living related partial liver transplantation. Over the subsequent 13-month follow-up, the patient's condition has remained fairly good.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
3/11. Localized proton MR spectroscopy in infants with urea cycle defect.SUMMARY: urea cycle defect is an inborn error of ammonium metabolism caused by a deficient activity of the enzymes involved in urea synthesis. Localized short-TE proton MR spectroscopy, performed in two infants who had citrullinemia and ornithine transcarbamylase deficiency, respectively, showed a prominent increase of glutamine/glutamate and lipid/lactate complex in both cases. N-acetylaspartate, total creatine, and myo-inositol were decreased in the infant with citrullinemia. Proton MR spectroscopy provided useful information for the diagnosis and understanding of the pathophysiology of urea cycle enzyme defect.- - - - - - - - - - ranking = 6keywords = cycle (Clic here for more details about this article) |
4/11. MRI in a case of adult-onset citrullinemia.A 42-year-old man presented with a history of repeated episodes of consciousness disturbance for 5 years. The MRI showed abnormally high signal intensities on T2-weighted images at bilateral cingulate gyri, temporal lobes and insular regions, mimicking the finding of herpes simplex encephalitis. hyperammonemia was disclosed. Serial work-up led to the diagnosis of adult-onset citrullinemia, deficiency of argininosuccinate synthetase. The clinical symptoms improved after diet control and medication. Follow-up MRI showed resolution of the abnormal signal intensities. The MRI findings of citrullinemia and other urea-cycle defects might be attributed to hyperammonemic encephalopathy, but the manifestations were varied. Similar distribution of the abnormalities in the MRI could be found in some reported cases and indicates probably vulnerable sites of hyperammonemic brain injury.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
5/11. CT findings in the infantile form of citrullinemia.citrullinemia is a rare autosomal recessive inborn error of the urea cycle due to a deficiency in argininosuccinic acid synthetase. We present two cases of the infantile form of citrullinemia in which CT revealed bilateral and symmetric corticosubcortical hypoattenuating areas, ulegyric changes, and atrophy in the frontal lobes, as well as atrophy in the gyrus cinguli, insulae, and temporal lobes.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
6/11. Moderate citrullinaemia without hyperammonaemia in a child with mutated and deficient argininosuccinate synthetase.In a patient with microcephaly, feeding problems and restlessness, moderately increased serum and urine citrulline concentrations were observed. Protein and allopurinol loading did not result in additional indications for a urea cycle defect. The diagnosis of citrullinaemia was made at both the enzyme and dna level, resulting from a novel mutation in the argininosuccinate synthetase gene. The fact that the patient has not suffered from severe deterioration, and that there were only minor abnormalities in metabolite concentrations, suggests that the argininosuccinate synthetase capacity was less affected in vivo than in vitro. in vitro nuclear magnetic resonance investigation suggested an active acetylation mechanism for citrulline. This case illustrates the importance of performing extensive biochemical and molecular investigations in order to reach a definitive diagnosis, particularly in instances of moderate citrullinaemia.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
7/11. Elevated plasma citrulline and arginine due to consumption of citrullus vulgaris (watermelon).A 19-month-old girl with developmental delay was found to have moderately elevated plasma citrulline and mildly elevated plasma arginine concentrations. Dietary history revealed that she consumed large quantities of watermelon (citrullus vulgaris), a fruit containing high free citrulline and arginine concentrations. In order to determine whether the patient's high watermelon intake could account for her elevated plasma citrulline and arginine concentrations, we studied the response of plasma citrulline and arginine to ingestion of watermelon in six healthy adult volunteers. All developed markedly elevated plasma citrulline (mean maximum 593 micromol/L, range 386-1069) and moderately elevated plasma arginine (mean maximum 199 micromol/L, range 128-251). physicians and laboratory personnel performing metabolic investigations should be aware of watermelon-induced citrullinaemia. Its hallmarks are elevated plasma citrulline, and to a lesser extent arginine, in the absence of orotic or arginosuccinic aciduria or hyperammonaemia. This phenomenon has implications for the management of patients with urea cycle and related disorders.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
8/11. Argininosuccinate synthetase deficiency: mutation analysis in 3 Thai patients.Remarkable improvements in public health, nutrition, hygiene, and availability of medical services in the last 20 years have significantly reduced infant and childhood mortality in thailand. Therefore, many rare and previously unidentified genetic disorders, which, in the past, usually led to the death of affected infants before a definitive diagnosis, have now been increasingly recognized. Recently, we identified three unrelated patients from thailand who suffered from citrullinemia, one of five inherited types of urea cycle disorders. All were diagnosed within their first few weeks of life. Biochemical analyses, including plasma amino acid and urine organic acid profiles, are consistent with argininosuccinate synthetase (ASS) deficiency. Extensive mutation study by direct genomic sequencing of ASS demonstrated a homozygous G117S mutation in one patient and homozygous R363W mutations in the other two families.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
9/11. Nutritional management of urea cycle disorders.Nutritional management of patients who have urea cycle disorders is one of the most challenging tasks in clinical nutrition. The degree to which protein intake should be restricted in urea cycle disorders requires complex calculations which depend on many variables such as specific enzyme defect, age-related growth rate, current health status, level of physical activity, amount of free amino acids administered, energy intake, residual urea cycle function, family lifestyle, use of nitrogen-scavenging medications, and the patient's eating behaviors. This paper presents two case histories and a series of recommendations outlining the nutrition management of urea cycle disorders. It also identifies difficulties that arise in the course of treatment, and suggests practical solutions for overcoming them.- - - - - - - - - - ranking = 8keywords = cycle (Clic here for more details about this article) |
10/11. Cirrhosis in an infant heterozygous for classical citrullinaemia.Classical citrullinaemia is caused by the inherited deficiency of argininosuccinate synthetase. Although varying degrees of liver involvement have been observed in urea cycle defects, including classical citrullinaemia, the co-existence of liver failure in a patient heterozygous for the disease has not been reported before. A female infant was investigated to find out the aetiology of early infantile liver failure. She was later found to be a heterozygote for the G390R mutation found in severe citrullinaemia patients. CONCLUSION: Classical citrullinaemia is a phenotypically heterogeneous disease, and observations for signs of its presence should be made even in heterozygotes.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
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