Blood Levels of Ammonia and Nitrogen Scavenging Amino Acids in Patients with Inherited Hyperammonemia

Tuchman, Mendel; Yudkoff, Marc

doi:10.1006/mgme.1998.2783

Cited by 40 publications

(23 citation statements)

References 11 publications

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“…Not surprisingly, blood levels of major nitrogen carriers, such as glutamine and alanine, were significantly decreased in individuals who received these agents. As observed previously [16], patients with proximal urea cycle disorders (CPS1 and OTC deficiency) display higher plasma levels of glutamine than those with distal disorders (AS, AL and ARG deficiency), probably reflecting the sequestration of waste nitrogen in citrulline, argininosiccinate or arginine, respectively.…”

Section: Discussionsupporting

confidence: 70%

Cross-sectional multicenter study of patients with urea cycle disorders in the United States

Tuchman

Lee

Lichter‐Konecki

et al. 2008

Molecular Genetics and Metabolism

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196

174

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Inherited urea cycle disorders comprise eight disorders (UCD), each caused by a deficiency of one of the protein that is essential for ureagenesis. We report on a cross sectional investigation to determine clinical and laboratory characteristics of patients with UCD in the United States. The data used for the analysis was collected at the time of enrollment of individuals with inherited UCD into a longitudinal observation study. The study has been conducted by the Urea Cycle Disorders Consortium (UCDC) within the Rare Diseases Clinical Research Network (RDCRN) funded by the National Institutes of Health. One hundred eighty three patients were enrolled into the study. Ornithine transcarbamylase (OTC) deficiency was the most frequent disorder (55%), followed by argininosuccinic aciduria (17%) and citrullinemia (11%). 79% of the participants were white (16% Latinos), and 6% were African American. Intellectual and developmental disabilities were reported in 39% with learning disabilities (35%) and half had abnormal neurological examination. 63% were on a protein restricted diet, 37% were on Na-phenylbutyrate and 5% were on Na-benzoate. 45% of OTC deficient patients were on L-citrulline, while most patients with citrullinemia (58%) and argininosuccinic (79%) were on L-arginine. Plasma levels of branched-chain amino acids were reduced in patients treated with ammonia scavenger drugs. Plasma glutamine levels were higher in proximal UCD disorders and in the neonatal type disease. The RDCRN allows comprehensive analyses of rare inherited UCD, their frequencies and current medical practices.

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Section: Discussionsupporting

confidence: 70%

Cross-sectional multicenter study of patients with urea cycle disorders in the United States

Tuchman

Lee

Lichter‐Konecki

et al. 2008

Molecular Genetics and Metabolism

Self Cite

196

174

View full text Add to dashboard Cite

show abstract

“…In particular, citrulline, arginine, and ornithine were not decreased, However, the ratio of plasma glutamine versus blood ammonia was unusually low (Fig 1), unlike that observed in patients with various urea cycle defects. 16 Plasma glutamate averaged 54 Ϯ 25 mol/L (controls: 30 Ϯ 14), and was therefore not decreased. Urinary orotic acid excretions were inconsistent; at no occasion did we find a striking increase.…”

Section: Resultsmentioning

confidence: 92%

Functional Hyperactivity of Hepatic Glutamate Dehydrogenase as a Cause of the Hyperinsulinism/Hyperammonemia Syndrome: Effect of Treatment

et al. 2000

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Objective. The combination of persistent hyperammonemia and hypoketotic hypoglycemia in infancy presents a diagnostic challenge. Investigation of the possible causes and regulators of the ammonia and glucose disposal may result in a true diagnosis and predict an optimum treatment. Patient. Since the neonatal period, a white girl had been treated for hyperammonemia and postprandial hypoglycemia with intermittent hyperinsulinism. Her blood level of ammonia varied from 100 to 300 μmol/L and was independent of the protein intake. Methods. Enzymes of the urea cycle as well as glutamine synthetase and glutamate dehydrogenase (GDH) were assayed in liver tissue and/or lymphocytes. Results. The activity of hepatic GDH was 874 nmol/(min·mg protein) (controls: 472–938). Half-maximum inhibition by guanosine triphosphate was reached at a concentration of 3.9 μmol/L (mean control values: .32). The ratio of plasma glutamine/blood ammonia was unusually low. Oral supplements withN-carbamylglutamate resulted in a moderate decrease of the blood level of ammonia. The hyperinsulinism was successfully treated with diazoxide. Conclusion. A continuous conversion of glutamate to 2-oxoglutarate causes a depletion of glutamate needed for the synthesis of N-acetylglutamate, the catalyst of the urea synthesis starting with ammonia. In addition, the shortage of glutamate may lead to an insufficient formation of glutamine by glutamine synthetase. As GDH stimulates the release of insulin, the concomitant hyperinsulinism can be explained. This disorder should be considered in every patient with postprandial hypoglycemia and diet-independent hyperammonemia.

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“…Glutamine increases nitrogen waste in the brain, causing brain damage. Its level is related to the level of ammonia [23,24]. Neonates with hyperammonemic encephalopathy already had extensive brain injuries at the onset, and these were followed by encephalomalacia and brain atrophy at an early age.…”

Section: Discussionmentioning

confidence: 99%

High prevalence of neonatal presentation in Korean patients with citrullinemia type 1, and their shared mutations

Lee

Kim

Heo

et al. 2013

Molecular Genetics and Metabolism

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Blood Levels of Ammonia and Nitrogen Scavenging Amino Acids in Patients with Inherited Hyperammonemia

Cited by 40 publications

References 11 publications

Cross-sectional multicenter study of patients with urea cycle disorders in the United States

Cross-sectional multicenter study of patients with urea cycle disorders in the United States

Functional Hyperactivity of Hepatic Glutamate Dehydrogenase as a Cause of the Hyperinsulinism/Hyperammonemia Syndrome: Effect of Treatment

High prevalence of neonatal presentation in Korean patients with citrullinemia type 1, and their shared mutations

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