{"orpha":238583,"name":"Hyperphenylalaninemia due to tetrahydrobiopterin deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Hyperphenylalaninemia due to BH4 deficiency"],"definition":"A disorder of pterin metabolism characterized by tetrahydrobiopterin (BH4) biosynthesis or recycling deficiencies, leading to central dopamine and serotonin deficiency, characterized by infantile-onset neurological disease of variable severity ranging from mild forms with minor neurological development to severe forms with hypotonia, developmental delay, complex movement disorder dominated by dystonia or dystonia parkinsonism.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-238583/","orphanet_url":"https://www.orpha.net/en/disease/detail/238583","names":{"fr":{"name":"Hyperphénylalaninémie par déficit en tétrahydrobioptérine","synonyms":["Hyperphénylalaninémie par déficit en BH4"],"definition":"Trouble du métabolisme des ptérines caractérisé par des déficits de la biosynthèse ou du recyclage de la tétrahydrobioptérine (BH4), entraînant un déficit central en dopamine et en sérotonine caractérisé par une atteinte neurologique à début infantile de sévérité variable allant de formes légères à type de développement neurologique mineur à des formes sévères à type d'hypotonie, de retard de développement, de mouvements anormaux complexes dominés par une dystonie ou une dystonie-parkinsonisme."},"de":{"name":"Hyperphenylalaninämie durch Tetrahydrobiopterin-Mangel","synonyms":["Hyperphenylalaninämie durch BH4-Mangel","Hyperphenylalaninämie, nicht-phenylketonurische"],"definition":"Eine Störung des Pterin-Stoffwechsels, die durch einen Mangel an Tetrahydrobiopterin (BH4) in der Biosynthese oder im Recycling gekennzeichnet ist und zu einem zentralen Dopamin- und Serotoninmangel führt. Sie ist gekennzeichnet durch eine neurologische Erkrankung im Kindesalter mit unterschiedlichem Schweregrad. Die Symptome reichen von leichten Formen mit unauffälliger neurologischer Entwicklung bis hin zu schweren Formen mit Hypotonie, Entwicklungsverzögerung und komplexen Bewegungsstörungen, die von Dystonie oder dystonischem Parkinsonismus dominiert werden."},"es":{"name":"Hiperfenilalaninemia por deficiencia de tetrahidrobiopterina","synonyms":["Hiperfenilalaninemia no fenilcetonúrica","Hiperfenilalaninemia por deficiencia de BH4"],"definition":"Es un trastorno del metabolismo de la pterina caracterizado por deficiencias de la biosíntesis o del reciclaje de tetrahidrobiopterina (BH4), que conduce a una deficiencia central de dopamina y serotonina. Está caracterizado por una enfermedad neurológica de inicio infantil de gravedad variable que va desde discreta afectación neurológica hasta formas graves con hipotonía y retraso del desarrollo, trastorno complejo del movimiento dominado por distonía o distonía-parkinsonismo."},"it":{"name":"Iperfenilalaninemia da deficit di tetraidrobiopterina","synonyms":["Iperfenilalaninemia da deficit di BH4","Iperfenilalaninemia da deficit di tetraidrobiopterina","Iperfenilalaninemia non fenilchetonurica"],"definition":"L'iperfenilalaninemia (HPA) da deficit di tetraidrobiopterina (BH4), nota anche come HPA maligna, è una malattia degli aminoacidi ad esordio neonatale. È caratterizzata dai segni clinici caratteristici della fenilchetonuria (PKA; si veda questo termine) ma in seguito se ne differenzia per l'insorgenza di sintomi neurologici, che comprendono la microcefalia, la disabilità intellettiva, l'ipotonia centrale, il ritardo dello sviluppo motorio, la spasticità periferica e le crisi epilettiche, che persistono nonostante il controllo metabolico della fenilalanina nel plasma."},"nl":{"name":"Hyperfenylalaninemie door deficiëntie van tetrahydrobiopterine","synonyms":["Hyperfenylalaninemie door BH4-deficiëntie","Niet-fenylketonurische hyperfenylalaninemie"],"definition":"Een stoornis van het metabolisme van pterine, gekenmerkt door deficiëntie van biosynthese of recyclage van tetrahydrobiopterine (BH4), wat leidt tot centrale deficiëntie van dopamine en serotonine, hetgeen gekenmerkt wordt door infantiel optredende neurologische ziekte met variabele ernst, gaande van mild met geringe neurologische ontwikkelingsstoornissen tot ernstig met hypotonie, ontwikkelingsachterstand, complexe bewegingsstoornis gedomineerd door dystonie of dystonie-parkinsonisme."},"pt":{"name":"Hiperfenilalaninemia por deficiência de tetrahidrobiopterina","definition":"Perturbação do metabolismo da pterina caracterizada por deficiência na biossíntese ou reciclagem da tetra-hidrobiopterina (BH4), levando a uma carência central de dopamina e serotonina, caracterizada por doença neurológica de início infantil de gravidade variável, que engloba formas ligeiras com perturbação no desenvolvimento neurológico até formas graves com hipotonia, perturbação do desenvolvimento, perturbação complexa do movimento dominada por distonia ou distonia parkinsoniana."},"pl":{"name":"Hiperfenyloalaninemia","synonyms":["Hiperfenylalaninemia nie związana z fenyloketonurią","Hiperfenyloalaninemia z powodu niedoboru BH4","Hiperfenyloalaninemia z powodu niedoboru tetrahydrobiopteryny"],"definition":"Zaburzenie metabolizmu pteryny, które charakteryzuje się niedoborami biosyntezy lub recyklingu tetrahydrobiopteryny (BH4), prowadzące do ośrodkowego niedoboru dopaminy i serotoniny. Powoduje chorobę neurologiczną o początku w wieku dziecięcym i różnym nasileniu, od łagodnych postaci z nieznacznie zaburzonym rozwojem, do postaci ciężkich z hipotonią, opóźnieniem rozwoju, złożonymi zaburzeniami ruchowymi, z dominującą dystonią lub parkinsonizmem dystonicznym."},"cs":{"name":"Hyperfenylalaninemie","synonyms":["Non-fenylketonurická hyperfenylalaninemie","Hyperfenylalaninémie způsobená BH4 deficitem","Hyperfenylalaninémie způsobená deficitem tetrahydrobiopterinu"]},"uk":{"name":"Гіперфенілаланінемія внаслідок дефіциту тетрагідробіоптерину","synonyms":["Гіперфенілаланінемія внаслідок дефіциту BH4"],"definition":"A disorder of pterin metabolism characterized by tetrahydropterin (BH4) biosynthesis or recycling deficiencies, leading to central dopamine and serotonin deficiency, characterized by infantile-onset neurological disease of variable severity ranging from mild forms with minor neurological development to severe forms with hypotonia, developmental delay, complex movement disorder dominated by dystonia or dystonia parkinsonism."},"zh":{"name":"四氢生物蝶呤缺乏性高苯丙氨酸血症","synonyms":["四氢生物蝶呤缺乏所致高苯丙氨酸血症"],"definition":"四氢生物喋呤（BH4）缺乏所致高苯丙氨酸血症（HPA），也称作恶性HPA，是一种新生儿期发病的氨基酸紊乱，临床表现为典型的苯丙酮尿症（PKA；见该词条），之后表现为小头畸形、智力障碍、中枢性张力低下、运动发育迟缓、周围性痉挛和癫痫发作等神经症状，在控制血浆苯丙氨酸代谢的情况下本病仍会发展和持续。"},"tr":{"name":"Tetrahidrobiopterin eksikliğine bağlı hiperfenilalaninemi","synonyms":["Fenilketonürik olmayan hiperfenilalaninemi","BH4 eksikliğine bağlı hiperfenilalaninemi"]}},"xrefs":[{"source":"OMIM","code":"233910","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"261630","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"261640","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"264070","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E70.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C59.01","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1659163210"},{"source":"MONDO","code":"0016543","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0751436","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"7751","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":309819,"name":"Disorder of pterin metabolism","classifications":[150,156,181]}],"children":[{"orpha":13,"name":"6-pyruvoyl-tetrahydropterin synthase deficiency","type":"Clinical subtype"},{"orpha":226,"name":"Dihydropteridine reductase deficiency","type":"Clinical subtype"},{"orpha":2102,"name":"GTP cyclohydrolase I deficiency","type":"Clinical subtype"},{"orpha":1578,"name":"Pterin-4 alpha-carbinolamine dehydratase deficiency","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"GCH1","name":"GTP cyclohydrolase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"4193","ensembl":"ENSG00000131979","omim":"600225","loci":["14q22.2"],"via":{"orpha":2102,"name":"GTP cyclohydrolase I deficiency"}},{"symbol":"PCBD1","name":"pterin-4 alpha-carbinolamine dehydratase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"9760199[PMID]","hgnc":"8646","ensembl":"ENSG00000166228","omim":"126090","loci":["10q22.1"],"via":{"orpha":1578,"name":"Pterin-4 alpha-carbinolamine dehydratase deficiency"}},{"symbol":"PTS","name":"6-pyruvoyltetrahydropterin synthase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"9689","ensembl":"ENSG00000150787","omim":"612719","loci":["11q23.1"],"via":{"orpha":13,"name":"6-pyruvoyl-tetrahydropterin synthase deficiency"}},{"symbol":"QDPR","name":"quinoid dihydropteridine reductase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"9744478[PMID]","hgnc":"9752","ensembl":"ENSG00000151552","omim":"612676","loci":["4p15.32"],"via":{"orpha":226,"name":"Dihydropteridine reductase deficiency"}}],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.22,"area":"Japan","status":"Validated","source":"6468444[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.2,"area":"Worldwide","status":"Validated","source":"[EXPERT]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.21,"area":"Brazil","status":"Validated","source":"35209917[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2024-10-29","source":"32456656[PMID]_33903016[PMID]_21937252[PMID]","terms":[{"hpo":"HP:0004923","label":"Hyperphenylalaninemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0040210","label":"Abnormal circulating biopterin concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040206","label":"Abnormal circulating neopterin concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040416","label":"Abnormal urinary nitrogen compound level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003785","label":"Decreased CSF homovanillic acid concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003781","label":"Excessive salivation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002135","label":"Basal ganglia calcification","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:6000482","label":"Decreased circulating catecholamine concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0033594","label":"Elevated urinary 7-biopterin level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002917","label":"Hypomagnesemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004904","label":"Maturity-onset diabetes of the young","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010553","label":"Oculogyric crisis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001300","label":"Parkinsonism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Occasional (29-5%)","criteria":null}]}}