{"orpha":415,"name":"Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["HHH syndrome","ORNT1 deficiency","Ornithine carrier deficiency","Ornithine translocase deficiency","Triple H syndrome"],"definition":"A rare, genetic disorder of urea cycle metabolism characterized by either a neonatal-onset with manifestations of lethargy, poor feeding, vomiting and tachypnea or, more commonly, presentations in infancy, childhood or adulthood with chronic neurocognitive deficits, acute encephalopathy and/or coagulation defects or other chronic liver dysfunction.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-415/","orphanet_url":"https://www.orpha.net/en/disease/detail/415","names":{"fr":{"name":"Syndrome d'hyperornithinémie-hyperammoniémie-homocitrullinurie","synonyms":["Déficit en ORNT1","Déficit en ornithine translocase","Syndrome HHH","Syndrome triple H"],"definition":"Trouble rare du métabolisme du cycle de l'urée d'origine génétique caractérisé soit par une apparition néonatale se manifestant par une léthargie, des difficultés à s'alimenter, des vomissements et une tachypnée, soit, dans des cas plus fréquents, par une apparition au cours de la petite enfance, de l'enfance ou à l'âge adulte, se manifestant par un déficit neurocognitif chronique, une encéphalopathie aiguë et/ou des troubles de la coagulation ou tout autre dysfonctionnement chronique du foie."},"de":{"name":"Hyperornithinämie-Hyperammonämie-Homocitrullinurie-Syndrom","synonyms":["HHH-Syndrom","ORNT1-Defizienz","ORNT1-Mangel","Ornithin-Translokase-Mangel","Ornithin-Transporter-Mangel","Triple-H-Syndrom"],"definition":"Eine seltene, genetisch bedingte Störung des Harnstoffzyklus-Stoffwechsels, die sich bereits im Neugeborenenstadium manifestieren kann und mit Lethargie, Stillproblemen, Erbrechen und Tachypnoe einhergeht. Häufiger beginnt es im Säuglings-, Kindes- oder Erwachsenenalter und ist gekennzeichnet durch chronisch neurokognitive Defizite, akuter Enzephalopathie und/oder Gerinnungsstörungen oder anderen chronischen Leberfunktionsstörungen."},"es":{"name":"Síndrome de hiperornitinemia-hiperamonemia-homocitrulinuria","synonyms":["Deficiencia de ORNT1","Deficiencia de ornitina translocasa","Deficiencia del transportador de la ornitina","Síndrome HHH","Síndrome de la triple H"],"definition":"Es un trastorno de origen genético y poco frecuente del ciclo de la urea caracterizado por un inicio neonatal con manifestaciones de letargia, problemas de alimentación, vómitos y taquipnea o, más frecuentemente, por presentación en el periodo de lactante, infancia o en edad adulta, con deficiencias neurocognitivas crónicas, encefalopatía aguda y/o trastornos de la coagulación u otras disfunciones hepáticas crónicas."},"it":{"name":"Sindrome iperornitinemia iperammoniemia-omocitrullinuria","synonyms":["Deficit del trasportatore dell'ornitina","Deficit di ORNT1","Sindrome HHH","Sindrome della tripla H"],"definition":"Si tratta di un difetto genetico raro del metabolismo del ciclo dell'urea. La malattia può esordire in epoca neonatale con letargia, difficoltà ad alimentarsi, vomito e tachipnea; oppure, più spesso, durante l'infanzia o l'età adulta con deficit neurocognitivi cronici, encefalopatia acuta e/o difetti della coagulazione o disfunzione epatica cronica."},"nl":{"name":"Hyperornithinemie - hyperammoniëmie - homocitrullinurie-syndroom","synonyms":["HHH-syndroom","ORNT1-deficiëntie","Ornithinetranslocase-deficiëntie","Ornithinetransporterdeficiëntie","Triple H-syndroom"],"definition":"Een zeldzame, genetische stoornis van ureumcyclus, gekarakteriseerd door ofwel een neonatale aanvang met manifestaties als lethargie, weinig eten, braken en tachypneu, ofwel, gangbaarder, aanvang in de zuigelingentijd, kindertijd of volwassenheid met chronische neurocognitieve defecten, acute encefalopathie en/of coagulatiedefecten of andere chronische leverdisfunctie."},"pt":{"name":"Síndrome de hiperornitinemia-hiperamoniemia-homocitrulinuria","synonyms":["Síndrome HHH","Síndrome de triplo H"]},"pl":{"name":"Zespół hiperornitynemii, hiperamonemii i homocytrulinemii","synonyms":["Niedobór nośnika ornityny","Niedobór ORNT1","Zespół HHH","Zespół potrójnego H"]},"cs":{"name":"Syndrom zahrnující hyperornitinemii, hyperamonemii a homocitrulinurii","synonyms":["HHH syndrom","Deficit ORNT1","Triple H syndrom","Deficit přenašeče ornitinu"]},"uk":{"name":"Синдром гіперорнітинемії-гіперамоніємії-гомоцитрулінурії","synonyms":["Синдром HHH","Дефіцит носія орнітину","Дефіцит орнітинової транслокази","Дефіцит ORNT1","Синдром потрійного Н"],"definition":"A rare, genetic disorder of urea cycle metabolism characterized by either a neonatal-onset with manifestations of lethargy, poor feeding, vomiting and tachypnea or, more commonly, presentations in infancy, childhood or adulthood with chronic neurocognitive deficits, acute encephalopathy and/or coagulation defects or other chronic liver dysfunction."},"zh":{"name":"高鸟氨酸血症-高氨血症-高瓜氨酸尿综合征","synonyms":["鸟氨酸移位酶缺乏症"]},"tr":{"name":"Hiperornitinemi-hiperamonemi-homositrülinüri sendromu","synonyms":["HHH sendromu","ORNT1 eksikliği","Üçlü H sendromu","Ornitin taşıyıcı eksikliği","Ornitin translokaz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"238970","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E72.4","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C50.AY","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1193271821"},{"source":"MONDO","code":"0009393","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C538380","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0268540","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"2830","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10084220","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":"SLC25A15","name":"solute carrier family 25 member 15","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"22649802[PMID]","hgnc":"10985","ensembl":"ENSG00000102743","omim":"603861","loci":["13q14.11"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Adolescent","Adult","Childhood","Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_25874378[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Europe","status":"Validated","source":"European Medicines Agency 2013[OTHER]"},{"type":"Cases/families","qualification":"Case(s)","class":null,"value":111.0,"area":"Worldwide","status":"Validated","source":"25874378[PMID]"},{"type":"Prevalence at birth","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"United States","status":"Validated","source":"23972786[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-04-08","source":"18978333[PMID]_11552031[PMID]_25874378[PMID]_22642880[PMID]_3116497[PMID]_5782534[PMID]","terms":[{"hpo":"HP:0011965","label":"Abnormality of citrulline metabolism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001987","label":"Hyperammonemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012026","label":"Hyperornithinemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006846","label":"Acute encephalopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002169","label":"Clonus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001289","label":"Confusion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001410","label":"Decreased liver function","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002572","label":"Episodic vomiting","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012115","label":"Hepatitis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002495","label":"Impaired vibratory sensation","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:0003218","label":"Oroticaciduria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002370","label":"Poor coordination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002073","label":"Progressive cerebellar ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002038","label":"Protein avoidance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001258","label":"Spastic paraplegia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001328","label":"Specific learning disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011098","label":"Speech apraxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002789","label":"Tachypnea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003256","label":"Abnormality of the coagulation cascade","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001259","label":"Coma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002123","label":"Generalized myoclonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007052","label":"Multifocal cerebral white matter abnormalities","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001950","label":"Respiratory alkalosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002064","label":"Spastic gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000533","label":"Chorioretinal atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0040030","label":"Chorioretinal hypopigmentation","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001399","label":"Hepatic failure","frequency":"Very rare (<4-1%)","criteria":null}]}}