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Journal of Pediatric Gastroenterology... Aug 2020Ornithine transcarbamylase deficiency (OTCD) is the most common of the urea cycle disorders and follows an X-linked inheritance pattern. The classical form in male...
Ornithine transcarbamylase deficiency (OTCD) is the most common of the urea cycle disorders and follows an X-linked inheritance pattern. The classical form in male infants causes vomiting and lethargy in the neonatal period; if untreated the severe hyperammonaemia can cause acute neurotoxic complications and permanent disability. OTCD may also occur in heterozygote female individuals, though the manifestations are variable. We report 2 cases of female paediatric patients with OTCD, who presented with acute liver failure. Both patients had limited oral intake at the time of presentation, causing an absence of orotic aciduria, which delayed the diagnosis. These cases demonstrate the need to consider urea cycle disorders in children presenting with acute liver failure, and that repeating the urine metabolic screen at the time of an unrestricted diet is warranted if there is a high clinical suspicion.
Topics: Child; Female; Heterozygote; Humans; Hyperammonemia; Infant; Infant, Newborn; Liver Failure, Acute; Ornithine Carbamoyltransferase Deficiency Disease
PubMed: 32265410
DOI: 10.1097/MPG.0000000000002716 -
PloS One 2015Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250) is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In...
Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250) is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In this report, we describe a new animal model of OTCD caused by a spontaneous mutation in the mouse Otc gene (c.240T>A, p.K80N). This transversion in exon 3 of ornithine transcarbamylase leads to normal levels of mRNA with low levels of mature protein and is homologous to a mutation that has also been described in a single patient affected with late-onset OTCD. With higher residual enzyme activity, spf-J were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to WT, spf-J displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic:polycytidylic acid. Our results indicate that the mild spf-J mutation constitutes a new mouse model that is suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans.
Topics: Amino Acid Sequence; Amino Acids; Animals; Biological Transport; Body Weight; Brain; Disease Models, Animal; Humans; Mice; Molecular Sequence Data; Mutation, Missense; Ornithine Carbamoyltransferase; Ornithine Carbamoyltransferase Deficiency Disease; Orotic Acid; Phenotype; Poly I-C; Protein Structure, Tertiary; Rats; Survival Analysis
PubMed: 25647322
DOI: 10.1371/journal.pone.0116594 -
Brain & Development Sep 2014Many females who are heterozygous for ornithine carbamoyltransferase (OTC) deficiency are asymptomatic or intermittently symptomatic with great phenotypic variability....
Many females who are heterozygous for ornithine carbamoyltransferase (OTC) deficiency are asymptomatic or intermittently symptomatic with great phenotypic variability. Therefore, the diagnosis of this condition is occasionally a challenge and is often delayed. A 12-year-old girl who was initially diagnosed as having attention deficit-hyperactivity disorder (ADHD) became comatose and developed right-sided hemiparesis during her psychiatric admission. Brain magnetic resonance imaging indicated diffuse but extensive swelling in the left hemisphere with multiple lesions suggestive of an old infarction. Repeated evaluations revealed hyperammonemia and orotic aciduria, and she was diagnosed as having an OTC deficiency. Genetic analysis revealed a heterozygous mutation of N47I in the X-linked OTC gene. Her mental status and hemiparesis improved after hyperammonemia treatment. Here, we report a rare case of a manifestating female carrier with severe symptoms of OTC deficiency masquerading as ADHD.
Topics: Attention Deficit Disorder with Hyperactivity; Brain; Child; Female; Heterozygote; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mutation; Ornithine Carbamoyltransferase; Ornithine Carbamoyltransferase Deficiency Disease
PubMed: 24199608
DOI: 10.1016/j.braindev.2013.09.009 -
JIMD Reports Jan 2021The combination of neonatal hyperammonemia, lactic acidosis, ketonuria, and hypoglycemia is pathognomonic for carbonic anhydrase VA (CA-VA) deficiency. We present two...
Two cases of carbonic anhydrase VA deficiency-An ultrarare metabolic decompensation syndrome presenting with hyperammonemia, lactic acidosis, ketonuria, and good clinical outcome.
The combination of neonatal hyperammonemia, lactic acidosis, ketonuria, and hypoglycemia is pathognomonic for carbonic anhydrase VA (CA-VA) deficiency. We present two cases of this rare inborn error of metabolism. Both newborns with South Asian ancestry presented with a metabolic decompensation characterized by hyperammonemia, lactic acidosis and ketonuria; one also had hypoglycemia. Standard metabolic investigations (plasma amino acids, acylcarnitine profile, and urine organic acids) were not indicative of a specific organic aciduria or fatty acid oxidation defect but had some overlapping features with a urea cycle disorder (elevated glutamine, orotic acid, and low arginine). Hyperammonemia was treated initially with nitrogen scavenger therapy and carglumic acid. One patient required hemodialysis. Both have had a favorable long-term prognosis after their initial metabolic decompensation. Genetic testing confirmed the diagnosis of carbonic anhydrase VA (CA-VA) deficiency due to biallelic pathogenic variants in . These cases are in line with 15 cases previously described in the literature, making the phenotypic presentation pathognomonic for this ultrarare (potentially underdiagnosed) inborn error of metabolism with a good prognosis.
PubMed: 33473334
DOI: 10.1002/jmd2.12171