Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management.

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle defect. The clinical presentation in female manifesting carriers varies both in onset and severity. We report on a female with insulin dependent diabetes mellitus and recurrent episodes of hyperammonemia.

Bacterial expression of mutant argininosuccinate lyase reveals imperfect correlation of in-vitro enzyme activity with clinical phenotype in argininosuccinic aciduria.

Background: The urea cycle defect argininosuccinate lyase (ASL) deficiency has a large spectrum of presentations from highly severe to asymptomatic. Enzyme activity assays in red blood cells or fibroblasts, although diagnostic of the deficiency, fail to discriminate between severe, mild or asymptomatic cases. Mutation/phenotype correlation studies are needed to characterize the effects of individual mutations on the activity of the enzyme.

Multisite analytical evaluation of the Abbott ARCHITECT cyclosporine assay.

The objective of this study was to evaluate the analytical performance of the Abbott ARCHITECT Cyclosporine (CsA) immunoassay in 7 clinical laboratories in comparison to liquid chromatography/tandem mass spectrometry (LC/MS/MS), Abbott TDx, Cobas Integra 800, and the Dade Dimension Xpand immunoassay. The ARCHITECT assay uses a whole blood specimen, a pretreatment step with organic reagents to precipitate proteins and extract the drug, followed by a 2-step automated immunoassay with magnetic microparticles coated with anti-CsA antibody and an acridinium-CsA tracer. Imprecision testing at the 7 evaluation sites gave a range of total % coefficient of variations of 7.

Mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients have recurrently arisen and have been retained in some populations.

We performed haplotype analysis using nine single nucleotide polymorphisms in the ornithine transcarbamylase gene to explore the ancestral origins of three mutations associated with late-onset phenotype in male patients: p.R40H, p.R277W and p.

Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency.

Introduction: N-Acetylglutamate synthase (NAGS) deficiency is a rare urea cycle disorder, which may present in the neonatal period with severe hyperammonemia and marked neurological impairment.

Case Report: We report on a Turkish family with a patient who died due to hyperammonemia in the neonatal period. Reduced activity of NAGS and carbamyl phosphate synthetase were found at autopsy.

Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency.

Background: Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of urea metabolism that can lead to hyperammonemic crises and orotic aciduria. To date, a total of 341 causative mutations within the OTC gene have been described. However, in about 20% of the patients with enzymatically confirmed OTC deficiency no mutation can be detected when sequencing of genomic DNA analyzing exons and adjacent intronic segments of the OTC gene is performed.

Differences in catalytic activity between rat testicular and ovarian carbonyl reductases are due to two amino acids.

The sequences of rat testis carbonyl reductase (rCR1) and rat ovary carbonyl reductase (rCR2) are 98% identical, differing only at amino acids 140, 141, 143, 235 and 238. Despite such strong sequence identity, we find that rCR1 and rCR2 have different catalytic constants for metabolism of menadione and 4-benzoyl-pyridine. Compared to rCR1, rCR2 has a 20-fold lower K(m) and 5-fold lower k(cat) towards menadione and a 7-fold lower K(m) and 7-fold lower k(cat) towards 4-benzoyl-pyridine.

Neonatal hyperammonemia: the N-carbamoyl-L-glutamic acid test.

In a prospective study, patients with a suspected urea cycle defect underwent oral N-carbamoyl-L-glutamic acid loading testing. In patients with subsequently confirmed N-acetylglutamate synthase deficiency, hyperammonemia normalized within 8 hours. This test may be useful in the early diagnosis of patients with suspected urea cycle disorders.

Identification of novel mutations of the human N-acetylglutamate synthase gene and their functional investigation by expression studies.

The mitochondrial enzyme N-acetylglutamate synthase (NAGS) produces N-acetylglutamate serving as an allosteric activator of carbamylphosphate synthetase 1, the first enzyme of the urea cycle. Autosomal recessively inherited NAGS deficiency (NAGSD) leads to severe neonatal or late-onset hyperammonemia. To date few patients have been described and the gene involved was described only recently.

Severe, neonatal-onset OTC deficiency in twin sisters with a de novo balanced reciprocal translocation t(X;5)(p21.1;q11).

OTC deficiency, the most common urea cycle defect, is transmitted as a partially dominant X-linked trait. The most severe form of the disease, however, is usually restricted to males. We report on monozygotic female twins with severe neonatal-onset OTC deficiency and a de novo balanced reciprocal translocation t(X;5)(p21.

Hyperammonaemia as a cause of psychosis in an adolescent.

Unlabelled: Diseases that cause hyperammonaemia usually appear during the neonatal period or during the first months of life as severe neurological metabolic distress. In some cases, as the one reported here, the age of onset and initial symptoms are non-specific and the episodes of acute metabolic encephalopathy may be attributed to encephalitis, poisoning or psychiatric problems. Our patient had N-acetyl glutamate synthetase deficiency due to a lack of activation by L-arginine.

Long-term calcineurin inhibition and magnesium balance after renal transplantation.

Regulation of magnesium balance is achieved by a steady-state mechanism in which intake and output are maintained at an equal level. Dietary magnesium intake, total and ionized plasma magnesium levels, and urinary magnesium were assessed in 46 renal transplant recipients treated with cyclosporine, nine transplant recipients who had never been on cyclosporine, and 31 healthy volunteers. Dietary magnesium intake [13.