{"orpha":1675,"name":"Dihydropyrimidine dehydrogenase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Familial pyrimidinemia"],"definition":"A rare disorder of pyrimidine metabolism characterized by a variable phenotype ranging from absence of symptoms to severe neurological involvement with developmental delay, intellectual disability, and seizures. Additional signs and symptoms may include hypotonia, microcephaly, ocular abnormalities (such as microphthalmia, nystagmus, and strabismus), and autistic behavior, among others. Analysis of urine typically shows high levels of uracil and thymine. Patients are at risk of suffering from severe toxicity after the administration of the anti-neoplastic agent 5-fluorouracil.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-1675/","orphanet_url":"https://www.orpha.net/en/disease/detail/1675","names":{"fr":{"name":"Déficit en dihydropyrimidine déshydrogénase","synonyms":["Pyrimidinémie familiale"],"definition":"Trouble rare du métabolisme de la pyrimidine caractérisé par un phénotype variable, allant d'une absence de symptômes à une atteinte neurologique sévère à type de retard de développement, de déficience intellectuelle et de crises convulsives. Les autres signes et symptômes peuvent inclure, entre autres, une hypotonie, une microcéphalie, des anomalies oculaires (microphtalmie, nystagmus et strabisme) et un comportement autistique. L'analyse des urines révèle généralement des concentrations élevées en uracile et en thymine. Les patients sont à risque de toxicité sévère après l'administration de 5-fluorouracile, un antinéoplasique."},"de":{"name":"Dihydropyrimidin-Dehydrogenase-Mangel","synonyms":["Pyrimidinämie, familiäre"],"definition":"Eine seltene Störung des Pyrimidin-Stoffwechsels, die durch einen variablen Phänotyp gekennzeichnet ist, der vom Fehlen von Symptomen bis hin zu einer schweren neurologischen Beteiligung mit Entwicklungsverzögerung, Intelligenzminderung und Krampfanfällen reicht. Weitere Anzeichen und Symptome können unter anderem Hypotonie, Mikrozephalie, Augenanomalien (wie Mikrophthalmie, Nystagmus und Strabismus) und autistisches Verhalten sein. Die Analyse des Urins zeigt in der Regel hohe Werte von Uracil und Thymin. Nach der Verabreichung des antineoplastischen Wirkstoffs 5-Fluorouracil besteht für die Patienten das Risiko einer schweren Toxizität."},"es":{"name":"Deficiencia de dihidropirimidina deshidrogenasa","definition":"Es un trastorno poco frecuente del metabolismo de las pirimidinas caracterizado por un fenotipo variable que va desde la ausencia de síntomas hasta la afectación neurológica grave con retraso del desarrollo, discapacidad intelectual y crisis. Otros posibles signos y síntomas incluyen hipotonía, microcefalia, anomalías oculares (como microftalmia, nistagmo y estrabismo) y conducta autista, entre otros. El análisis de orina suele mostrar niveles elevados de uracilo y timina. Los pacientes corren el riesgo de experimentar toxicidad grave tras la administración del agente antineoplásico 5-fluorouracilo."},"it":{"name":"Deficit di diidropirimidina deidrogenasi","synonyms":["Pirimidinemia familiare"],"definition":"Si tratta di una malattia rara del metabolismo delle pirimidine, caratterizzata da un fenotipo variabile che comprende i pazienti completamente asintomatici, fino al grave coinvolgimento neurologico con ritardo nello sviluppo, disabilità intellettiva e crisi epilettiche. I pazienti possono presentare ipotonia, microcefalia, anomalie oculari (microftalmia, nistagmo, strabismo) e tratti autistici. L'esame delle urine in genere evidenzia livelli elevati di uracile e timina. I pazienti sono a rischio di grave tossicità dopo la somministrazione dell'agente antineoplastico 5-fluorouracile."},"nl":{"name":"Deficiëntie van dihydropyrimidine-dehydrogenase","synonyms":["Familiale pyrimidinemie"],"definition":"Een zeldzame aandoening van pyrimidinemetabolisme, gekarakteriseerd door een variabel fenotype gaande van afwezigheid van symptomen tot ernstige neurologische betrokkenheid met ontwikkelingsachterstand, intellectuele achterstand, en insulten. Mogelijke bijkomende verschijnselen en symptomen zijn onder meer hypotonie, microcefalie, ooganomalieën (zoals microftalmie, nystagmus, en strabisme), en autistisch gedrag. Analyse van urine toont doorgaans hoge gehaltes van uracil en thymine. Patiënten lopen risico op ernstige toxiciteit na toediening van het antineoplastische middel 5-fluoro-uracil."},"pt":{"name":"Deficiência de diidropirimidina desidrogenase","synonyms":["Pirimidinemia familiar"]},"pl":{"name":"Niedobór dyhydrogenazy dihydropirymidynowej","synonyms":["Pirymidynemia rodzinna"]},"cs":{"name":"Deficit dihydropyrimidin dehydrogenázy","synonyms":["Familiární pyrimidinémie"]},"uk":{"name":"Дефіцит дигідропіримідиндегідрогенази","synonyms":["Сімейна піримідинемія"],"definition":"A rare disorder of pyrimidine metabolism characterized by a variable phenotype ranging from absence of symptoms to severe neurological involvement with developmental delay, intellectual disability, and seizures. Additional signs and symptoms may include hypotonia, microcephaly, ocular abnormalities (such as microphthalmia, nystagmus, and strabismus), and autistic behavior, among others. Analysis of urine typically shows high levels of uracil and thymine. Patients are at risk of suffering from severe toxicity after the administration of the anti-neoplastic agent 5-fluorouracil."},"zh":{"name":"二氢嘧啶脱氢酶缺乏症","synonyms":["家族性嘧啶血症"]},"tr":{"name":"Dihidropirimidin dehidrojenaz eksikliği","synonyms":["Ailesel pirimidinemi"]}},"xrefs":[{"source":"OMIM","code":"274270","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E79.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C55.1","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"701689290"},{"source":"MONDO","code":"0010130","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D054067","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1959620","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"19","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10052622","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79193,"name":"Disorder of pyrimidine metabolism","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]}],"children":[],"genes":[{"symbol":"DPYD","name":"dihydropyrimidine dehydrogenase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"3012","ensembl":"ENSG00000188641","omim":"612779","loci":["1p21.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["All ages"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-07-01","source":"19296131[PMID]_28275972[PMID]_16176880[PMID]","terms":[{"hpo":"HP:0003654","label":"Reduced dihydropyrimidine dehydrogenase activity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012127","label":"Uraciluria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010841","label":"Multifocal epileptiform discharges","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:0012433","label":"Abnormal social behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000478","label":"Abnormality of the eye","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000718","label":"Aggressive behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001284","label":"Areflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000483","label":"Astigmatism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006191","label":"Deep palmar crease","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002002","label":"Deep philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000684","label":"Delayed eruption of teeth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002656","label":"Epiphyseal dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002373","label":"Febrile seizure (within the age range of 3 months to 6 years)","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011153","label":"Focal motor seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030890","label":"Hyperintensity of cerebral white matter on MRI","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002187","label":"Intellectual disability, profound","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000737","label":"Irritability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009748","label":"Large earlobe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000527","label":"Long eyelashes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001104","label":"Macular hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000482","label":"Microcornea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002983","label":"Micromelia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000194","label":"Open mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030939","label":"Palpebral thickening","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002033","label":"Poor suck","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011220","label":"Prominent forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005274","label":"Prominent nasal tip","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004887","label":"Respiratory failure requiring assisted ventilation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000278","label":"Retrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006863","label":"Severe expressive language delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001799","label":"Short nail","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null}]}}