{"orpha":23,"name":"Argininosuccinic aciduria","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["ASA deficiency","ASL deficiency","Argininosuccinase deficiency","Argininosuccinatelyase deficiency","Argininosuccinic acid lyase deficiency"],"definition":"A rare, genetic disorder of urea cycle metabolism typically characterized by either a severe, neonatal-onset form that manifests with hyperammonemia accompanied with vomiting, hypothermia, lethargy and poor feeding in the first few days of life, or late-onset forms that manifest with stress- or infection-induced episodic hyperammonemia or, in some, behavioral abnormalities and/or learning disabilities, or chronic liver disease. Patients often manifest liver dysfunction.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-23/","orphanet_url":"https://www.orpha.net/en/disease/detail/23","names":{"fr":{"name":"Acidurie argininosuccinique","synonyms":["ASA","Déficit en ASL","Déficit en acide arginosuccinique synthétase","Déficit en argininosuccinase","Déficit en argino-succinate lyase"],"definition":"Trouble rare du métabolisme du cycle de l'urée, d'origine génétique, généralement caractérisé soit par une forme grave à début néonatal qui se manifeste par une hyperammoniémie accompagnée de vomissements, d'une hypothermie, d'une léthargie et de difficultés à s'alimenter au cours des premiers jours de vie, soit par des formes à début tardif qui se manifestent par des épisodes d'hyperammoniémie induits par le stress ou par une infection ou, chez certains, par des troubles du comportement et/ou des difficultés d'apprentissage, ou par une maladie hépatique chronique. Les patients présentent souvent un dysfonctionnement hépatique."},"de":{"name":"Argininbernsteinsäure-Krankheit","synonyms":["ASL-Mangel","Argininosuccinase-Mangel","Argininsuccinat-Lyase-Mangel","Argininosuccinoazidurie"],"definition":"Eine seltene genetische Störung des Harnstoffzyklus-Stoffwechsels, die typischerweise entweder durch eine schwere neonatale Form mit Hyperammonämie in Verbindung mit Erbrechen, Hypothermie, Lethargie und schlechter Nahrungsaufnahme in den ersten Lebenstagen oder eine späte Form mit stress- oder infektionsbedingter episodischer Hyperammonämie oder in einigen Fällen mit Verhaltensauffälligkeiten und/oder Lernbehinderungen oder chronischen Lebererkrankungen gekennzeichnet ist. Die Patienten weisen häufig eine Leberfunktionsstörung auf."},"es":{"name":"Aciduria argininosuccínica","synonyms":["Deficiencia ASA","Deficiencia ASL","Deficiencia de argininosuccinato liasa","Deficiencia de arginosuccinasa","Deficiencia de ácido argininosuccínico liasa"],"definition":"Es un trastorno del metabolismo del ciclo de la urea, de origen genético y poco frecuente, caracterizado típicamente por una forma grave de inicio neonatal que se manifiesta en los primeros días de vida como hiperamonemia acompañada de vómitos, hipotermia, letargia y problemas de la alimentación, o por formas de inicio tardío que se manifiestan como hiperamonemia episódica inducida por infecciones o estrés o, en algunos casos, como alteraciones de la conducta y/o dificultades de aprendizaje, o como enfermedad hepática crónica. A menudo, los pacientes manifiestan disfunción hepática."},"it":{"name":"Aciduria argininosuccinica","synonyms":["Deficit della liasi dell'acido argininosuccinico","Deficit di ASA","Deficit di ASL","Deficit di argininosuccinasi","Deficit di argininosuccinato liasi"],"definition":"L'aciduria argininosuccinica (ASA) è un difetto genetico raro del metabolismo del ciclo dell'urea, caratterizzato da una forma grave ad esordio neonatale che si manifesta nei primi giorni di vita con iperammoniemia associata a vomito, ipotermia, letargia e difficoltà di alimentazione, oppure da forme ad esordio tardivo, che si manifestano con iperammoniemia episodica scatenata dallo stress o dalle infezioni, oppure, in alcuni pazienti, con anomalie comportamentali e/o difficoltà di apprendimento, o con epatopatia cronica. I pazienti spesso presentano una disfunzione epatica."},"nl":{"name":"Argininobarnsteenzuuracidurie","synonyms":["ASA-deficiëntie","ASL-deficiëntie","Argininobarnsteenzuurlyasedeficiëntie","Argininosuccinaatlyasedeficiëntie","Argininosuccinasedeficiëntie"],"definition":"Een zeldzame, genetische aandoening van ureumcyclus, doorgaans gekarakteriseerd door ofwel een ernstige, neonataal aanvangende vorm die zich manifesteert met hyperammoniëmie vergezeld van braken, hypothermie, lethargie en weinig eten tijdens de eerste levensdagen, ofwel laat aanvangende vormen die zich manifesteren met door stress of infectie geïnduceerde episodische hyperammoniëmie of, bij sommigen, met gedragsstoornissen en/of leerbeperkingen, of chronische leverziekte. Patiënten vertonen vaak leverdisfunctie."},"pt":{"name":"Acidúria argininosuccínica","synonyms":["Deficiência de argininosuccinase"],"definition":"Doença genética rara do metabolismo do ciclo da ureia, tipicamente caracterizada por uma forma grave de início neonatal que se manifesta com hiperamonémia acompanhada de vómitos, hipotermia, letargia e dificuldade alimentares nos primeiros dias de vida, ou por formas de início tardio que se manifestam com hiperamonémia episódica induzida por stress ou infecção ou, em alguns casos, anomalias comportamentais e/ou dificuldades de aprendizagem, ou doença hepática crónica. Os doentes apresentam frequentemente disfunção hepática."},"pl":{"name":"Kwasica argininobursztynianowa","synonyms":["Niedobór argininosukcynazy","Niedobór ASA","Niedobór ASL","Niedobór liazy argininobursztynianowej","Niedobór liazy kwasu argininobursztynowego"],"definition":"Rzadkie, genetycznie uwarunkowane zaburzenie cyklu mocznikowego, które charakteryzuje się wystąpieniem ciężkiego zespołu u noworodków, z hiperamonemią, z towarzyszącymi wymiotami, hipotermią, sennością oraz zaburzeniami odżywiania w pierwszych dniach życia, lub postaciami o późnym początku z epizodyczną hiperamonemią wywołaną stresem lub infekcją lub, w niektórych przypadkach, zaburzeniami zachowania i/lub trudnościami w uczeniu lub przewlekłą chorobą wątroby. Często występują zaburzenia czynności wątroby."},"cs":{"name":"Argininsukcinátová acidurie","synonyms":["Deficit ASA","Deficit ASL","Deficit argininsukcinázy","Deficit argininosukcinátlyázy","Deficit argininsukcinátlyázy"]},"uk":{"name":"Аргінінобурштинова ацидурія","synonyms":["Дефіцит аргініносукцинази","Дефіцит аргініносукцинатеази","Дефіцит ліази аргінінобурштинової кислоти","Дефіцит ASA","Дефіцит ASL"],"definition":"A rare, genetic disorder of urea cycle metabolism typically characterized by either a severe, neonatal-onset form that manifests with hyperammonemia accompanied with vomiting, hypothermia, lethargy and poor feeding in the first few days of life, or late-onset forms that manifest with stress- or infection-induced episodic hyperammonemia or, in some, behavioral abnormalities and/or learning disabilities, or chronic liver disease. Patients often manifest liver dysfunction."},"zh":{"name":"精氨基琥珀酸尿","synonyms":["精氨基琥珀酸裂合酶缺乏症"]},"tr":{"name":"Arjininosukinik asidüri","synonyms":["ASA eksikliği","ASL eksikliği","Arjininosüksinaz eksikliği","Arjininosüksinatilaz eksikliği","Arjininosüksinik asit liyaz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"207900","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E72.2","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5C50.A0","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"439383288"},{"source":"MONDO","code":"0008815","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D056807","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0268547","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"5843","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10058299","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":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"ASL","name":"argininosuccinate lyase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"12384776[PMID]_21290785[PMID]","hgnc":"746","ensembl":"ENSG00000126522","omim":"608310","loci":["7q11.21"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["All ages"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.46,"area":"United States","status":"Validated","source":"23972786[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.69,"area":"Finland","status":"Validated","source":"18616627[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 100 000","value":1.0,"area":"Europe","status":"Validated","source":"European Medicines Agency 2019[OTHER]_[EXPERT]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.05,"area":"Austria","status":"Validated","source":"20236848[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2024-05-27","source":"21290785[PMID]_30723942[PMID]","terms":[{"hpo":"HP:0003355","label":"Aminoaciduria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001987","label":"Hyperammonemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003217","label":"Hyperglutaminemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0005961","label":"Hypoargininemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0025630","label":"Argininosuccinic aciduria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002329","label":"Drowsiness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011966","label":"Elevated plasma citrulline","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000822","label":"Hypertension","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0032491","label":"Increased circulating argininosuccinic acid","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0032470","label":"Monilethrix","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001950","label":"Respiratory alkalosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001328","label":"Specific learning disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002789","label":"Tachypnea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011362","label":"Abnormal hair quantity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011675","label":"Arrhythmia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007018","label":"Attention deficit hyperactivity disorder","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000670","label":"Carious teeth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006280","label":"Chronic pancreatitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001394","label":"Cirrhosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002014","label":"Diarrhea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000964","label":"Eczematoid dermatitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007183","label":"Focal T2 hyperintense basal ganglia lesion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002283","label":"Global brain atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001399","label":"Hepatic failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001395","label":"Hepatic fibrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002155","label":"Hypertriglyceridemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002900","label":"Hypokalemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003218","label":"Oroticaciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002232","label":"Patchy alopecia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006970","label":"Periventricular leukomalacia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003777","label":"Pili torti","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000709","label":"Psychosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000083","label":"Renal insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000742","label":"Self-mutilation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001894","label":"Thrombocytosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009886","label":"Trichorrhexis nodosa","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001402","label":"Hepatocellular carcinoma","frequency":"Very rare (<4-1%)","criteria":null}]}}