{"orpha":927,"name":"Hyperammonemia due to N-acetylglutamate synthase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["NAGS deficiency"],"definition":"A rare disorder of urea cycle metabolism causing a deficit of ammonia detoxification and arginine synthesis, and characterized by hyperammonemia of variable severity. Manifestations range from neonatal presentation of poor feeding, vomiting, lethargy, tachypnea, convulsions and coma to adult-onset headaches, hazy gastrointestinal symptoms, seizures, behavioral/psychiatric problems, confusion and lethargy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-927/","orphanet_url":"https://www.orpha.net/en/disease/detail/927","names":{"fr":{"name":"Hyperammoniémie par déficit en N-acétylglutamate synthase","synonyms":["Déficit en NAGS"],"definition":"Trouble rare du métabolisme du cycle de l'urée à l'origine d'un défaut de détoxification de l'ammoniac et de synthèse de l'arginine, caractérisé par une hyperammoniémie de sévérité variable. Les manifestations vont d'une présentation néonatale avec difficultés à s'alimenter, vomissements, léthargie, tachypnée, convulsions et coma, à une présentation à l'âge adulte avec céphalées, symptômes gastro-intestinaux non spécifiques, convulsions, problèmes comportementaux/psychiatriques, confusion et léthargie."},"de":{"name":"Hyperammonämie durch N-Acetylglutamat-Synthetase-Mangel","synonyms":["NAGS-Mangel"],"definition":"Eine seltene Störung des Harnstoffzyklus-Stoffwechsels, die ein Defizit der Ammoniak-Entgiftung und der Arginin-Synthese verursacht und durch eine Hyperammonämie unterschiedlichen Schweregrades gekennzeichnet ist. Die Manifestationen reichen von schlechter Nahrungsaufnahme, Erbrechen, Lethargie, Tachypnoe, Krämpfen und Koma bei Neugeborenen bis hin zu Kopfschmerzen, unklaren gastrointestinalen Symptomen, Krampfanfällen, Verhaltens- und psychiatrischen Problemen, Verwirrung und Lethargie bei Erwachsenen."},"es":{"name":"Hiperamonemia por deficiencia de N-acetilglutamato sintasa","synonyms":["Deficiencia de NAGS"],"definition":"Es un trastorno poco frecuente del metabolismo del ciclo de la urea que causa un déficit en la desintoxicación de amoníaco y la síntesis de arginina, caracterizado por hiperamonemia de gravedad variable. Las manifestaciones varían desde la presentación neonatal de problemas de alimentación, vómitos, letargia, taquipnea, convulsiones y coma, a dolores de cabeza de inicio en el adulto, síntomas digestivos vagos, crisis epilépticas, trastornos psiquiátricos/de la conducta, confusión y letargia."},"it":{"name":"Iperammoniemia da deficit di N-acetilglutammato sintasi","synonyms":["Deficit di NAGS"]},"nl":{"name":"Hyperammoniëmie door deficiëntie van N-acetylglutamaatsynthetase","synonyms":["NAGS-deficiëntie"],"definition":"Een zeldzame stoornis van metabolisme van ureumcyclus die gebrekkige detoxificatie van ammonium en synthese van arginine veroorzaakt, en gekenmerkt wordt door hyperammoniëmie met variabele ernst. Manifestaties gaan van neonatale presentatie van voedingsproblemen, braken, lethargie, tachypneu, convulsies en coma tot in de volwassenheid optredende hoofdpijn, vage gastro-intestinale symptomen, insulten, gedragsproblemen/psychiatrische problemen, verwardheid en lethargie."},"pt":{"name":"Hiperamoniemia devida a deficiência de N-acetilglutamato sintetase","synonyms":["Deficiência de N-acetilglutamato sintetase"],"definition":"Doença rara do metabolismo do ciclo da ureia que causa défice na desintoxicação da amónia e na síntese de arginina, e é caracterizado por hiperamonemia de gravidade variável. As manifestações variam desde uma apresentação neonatal de dificuldades alimentares, vómitos, letargia, taquipnéia, convulsões e coma até dores de cabeça na idade adulta, sintomas gastrointestinais inespecíficos, convulsões, perturbações comportamentais/psiquiátricas, confusão e letargia."},"pl":{"name":"Hiperammonemia spowodowana niedoborem syntetazy N-acetyloglutaminowej","synonyms":["Niedobór NAGS"]},"cs":{"name":"Hyperamonémie způsobená deficitem N-acetylglutamát syntázy","synonyms":["NAGS deficit"]},"uk":{"name":"Гіперамоніємія внаслідок дефіциту N-ацетилглутаматсинтази","synonyms":["Дефіцит NAGS"],"definition":"A rare disorder of urea cycle metabolism causing a deficit of ammonia detoxification and arginine synthesis, and characterized by hyperammonemia of variable severity. Manifestations range from neonatal presentation of poor feeding, vomiting, lethargy, tachypnea, convulsions and coma to adult-onset headaches, hazy gastrointestinal symptoms, seizures, behavioral/psychiatric problems, confusion and lethargy."},"zh":{"name":"N-乙酰谷氨酸合成酶缺乏所致高氨血症","synonyms":["NAGS缺乏症"]},"tr":{"name":"N-asetilglutamat sentaz eksikliğine bağlı hiperamonyemi","synonyms":["NAGS eksikliği"]}},"xrefs":[{"source":"OMIM","code":"237310","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E72.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C50.AY","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"812653109"},{"source":"MONDO","code":"0009377","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536109","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0268543","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"7158","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10071092","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79167,"name":"Disorder of urea cycle metabolism and ammonia detoxification","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"NAGS","name":"N-acetylglutamate synthase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301316[PMID]","hgnc":"17996","ensembl":"ENSG00000161653","omim":"608300","loci":["17q21.31"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["All ages"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Europe","status":"Validated","source":"ORPHANET"},{"type":"Cases/families","qualification":"Case(s)","class":null,"value":99.0,"area":"Worldwide","status":"Validated","source":"33036647[PMID]_33231058[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-04-25","source":"29364180[PMID]_30337552[PMID]_27147233[PMID]_27570737[PMID]","terms":[{"hpo":"HP:0001987","label":"Hyperammonemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002018","label":"Nausea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008281","label":"Acute hyperammonemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000713","label":"Agitation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000739","label":"Anxiety","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001259","label":"Coma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001289","label":"Confusion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002329","label":"Drowsiness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000712","label":"Emotional lability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012378","label":"Fatigue","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002315","label":"Headache","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003348","label":"Hyperalaninemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003217","label":"Hyperglutaminemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100785","label":"Insomnia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007185","label":"Loss of consciousness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004396","label":"Poor appetite","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002637","label":"Cerebral ischemia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0031258","label":"Delirium","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002014","label":"Diarrhea","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0010529","label":"Echolalia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002863","label":"Myelodysplasia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0010550","label":"Paraplegia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001271","label":"Polyneuropathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000725","label":"Psychotic episodes","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002098","label":"Respiratory distress","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0006582","label":"Reye syndrome-like episodes","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001297","label":"Stroke","frequency":"Very rare (<4-1%)","criteria":null}]}}