"Orotic aciduria"

Xuriden (uridine triacetate) - To treat patients with hereditary orotic aciduria Xuriden (uridine triacetate) oral granules * Skip to main page content * Skip to search * Skip to topics menu * Skip to common linksHHS U.S. Department of Health and Human Services U.S. Food and Drug Administration * Follow FDA * En EspañolSearch FDASubmit search * Popular Content * Home * Food * Drugs * Medical

Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue. We identified mild and isolated

in this topic.Jack Metz, MB, BCh, MD, DSc(Med), FRCPath, FCAP, FRCPA, FRS(SA), DSc Med(Hon Caus)Emeritus Professor and Consultant HaematologistDorevitch PathologyHeidelbergVictoriaAustraliaDisclosuresJM declares that he has no competing interests. * * Differentials * Vitamin B12 (cobalamin) deficiency * Thiamine-responsive megaloblastic anaemia * Hereditary orotic aciduria More Differentials

Recommendation on Regulatory ActionI recommend approval action for uridine triacetate for treatment of hereditary orotic aciduria” (HOA). Currently, there are no approved therapies for the disease. 1.2 Risk Benefit AssessmentThe benefit-risk analysis of uridine triacetate for the proposed indication is favorable. This is based ona review ofretrospective case studies of 18 patients with HOA treated uridine(1 1Bailey CJ, Orotic aciduria and uridine monophosphate synthase, J Inherit Metab Dis2009; 32 (Suppl 1): S227-S233.2Webster DR., Becroft DM et al., Hereditary Orotic Aciduria and Other Disorders of Pyrimidine Metabolism, Scriver’s Online Metabolic & Molecular Bases of Inherited Disease2001, Chapter 113: 1-86.3Huguley CM, Bain JA et al., Refractory

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

describe a patient who presented with a 2-year progression of waxing and waning acute mental status changes after a Roux-en-Y gastric bypass surgery. He was found to have elevated ammonia level as well as orotic aciduria; results consistent with a urea cycle disorder. After consulting neurology as well as toxicology, he ultimately improved after dietary protein restriction, sodium benzoate and lactulose

orotic aciduria (see Etiology).Treatment of megaloblastic anemia depends on the underlying cause. Supplemental folate or vitamin B-12 may be indicated (see Treatment).Go to Pediatric Chronic Anemia, Anemia of Prematurity, Donath-Landsteiner Hemolytic Anemia, Pediatric Acute Anemia, and Fanconi Anemia for complete information on these topics.Vitamin B-12 deficiencyVitamin B-12 is commonly ingested

orotic aciduria (see Etiology).Treatment of megaloblastic anemia depends on the underlying cause. Supplemental folate or vitamin B-12 may be indicated (see Treatment).Go to Pediatric Chronic Anemia, Anemia of Prematurity, Donath-Landsteiner Hemolytic Anemia, Pediatric Acute Anemia, and Fanconi Anemia for complete information on these topics.Vitamin B-12 deficiencyVitamin B-12 is commonly ingested

UniversityLast full review/revision Oct 2021 Click here for Patient Education * Uridine monophosphate synthase deficiency (hereditary orotic aciduria) * More Information Topic Resources * 3D Models (0) * Audios (0) * Calculators (0) * Images (0) * Lab Test (0) * Tables (1) Pyrimidine Metabolism Disorders * Videos (0) Pyrimidines may be synthesized de novo or recycled of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more .Table Uridine monophosphate synthase deficiency (hereditary orotic aciduria) Uridine monophosphate is the enzyme that catalyzes orotate phosphoribosyltransferase and orotidine-5′-monophosphate decarboxylase reactions

such as hydroxyurea, or immunosuppressants) that interfere with DNA synthesis and rare metabolic disorders (eg, hereditary orotic aciduria). Pathophysiology Megaloblastic states result from defective DNA synthesis. RNA synthesis continues, resulting in a large cell with a large nucleus. All cell lines have dyspoiesis, in which cytoplasmic maturity is greater than nuclear maturity; this dyspoiesis produces

Molecular mechanisms underlying large genomic deletions in ornithine transcarbamylase (OTC) gene. Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle error causing hyperammonemia and orotic aciduria. Clinical diagnosis is generally confirmed by mutation detection. However, in approximately 20% of the patients, no mutation is found by conventional mutation-searching strategies

: * orotic aciduria Lesch-Nyhan syndrome homocystinuria methylmalonic aciduria * acquired: * myelodysplasia metabolic inhibition by drugs: * 6-mercaptopurine * azathioprine * ganciclovir * aciclovir * fluorouracil * hydroxycarbamide (former British Approved Name, hydroxyurea) * cytosine arabinoside * cyclophosphamide Last reviewed 01/2018Links: * vitamin B12 deficiency

United States Australia Ireland Round-up MCQsGEMsAbout us TV Podcast Study Groups Shortcuts megaloblastic anaemia FREE subscriptions for doctors and students... click here You have 3 more open access pages. Common causes include: * vitamin B12 deficiency * folate deficiency Rare causes include: * inherited: * orotic aciduria Lesch-Nyhan syndrome homocystinuria methylmalonic aciduria * acquired

United States Australia Ireland Round-up MCQsGEMsAbout us TV Podcast Study Groups Shortcuts anemia (megaloblastic) FREE subscriptions for doctors and students... click here You have 3 more open access pages. Common causes include: * vitamin B12 deficiency * folate deficiency Rare causes include: * inherited: * orotic aciduria Lesch-Nyhan syndrome homocystinuria methylmalonic aciduria * acquired

be included in the differential diagnosis of acute postpartum coma. Hyperammonemia, hyperglutaminemia, and orotic aciduria are diagnostic, facilitate early treatment, and mitigate the risk of permanent neurologic impairment or death.

Anabolism * Orotic aciduria * Miller syndrome Catabolism * Dihydropyrimidine dehydrogenase deficiency * v * t

hyperammonemia and associated neurological impairment. Using this system, we showed that the dose of an AAV rescue construct encoding the murine OTC (mOTC) cDNA required to prevent hyperammonemia is fivefold lower than that required to control orotic aciduria. This result is favorable for clinical translation as it indicates that the threshold for therapeutic benefit is likely to be lower than indicated

Patient selection may affect gene therapy success. Dominant negative effects observed for ornithine transcarbamylase in mouse and human hepatocytes. We have achieved significant improvement of ornithine transcarbamylase deficiency (OTCD) in a mouse model through adenoviral-mediated gene transfer of the human ornithine transcarbamylase cDNA. Substantial reduction in orotic aciduria was observed

did not interfere with carbamyl phosphate synthesis as manifested by orotic aciduria. It is concluded that arginine is an indispensable amino acid for children with inborn errors of ureagenesis and its absence results in the rapid onset of symptomatic hyperammonemia.

Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC). Loss of either enzymatic activity results in hereditary orotic aciduria, a rare autosomal recessive disorder characterized by retarded growth, anemia, and excessive urinary excretion of orotic acid. We have isolated the UMP synthase chromosomal gene from a lambdaEMBL-3 human genomic library and report a single-copy gene spanning approximately 15 kb. The UMP synthase genomic structure encodes six exons ranging in size from 115 bp to 672 bp, and all