{"orpha":300,"name":"Bifunctional enzyme deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare peroxisomal beta-oxidation disorder characterized by deficiency of peroxisomal D-bifunctional protein, type 1 being caused by deficiency of both dehydrogenase and hydratase activities of the enzyme, and types 2 and 3 by hydratase or dehydrogenase deficiency alone, while type 4 is due to compound heterozygous mutations affecting both units and represents a clinically milder phenotype. Types 1-3 are typically fatal in infancy. Patients present with early onset of generalized hypotonia, seizures, severe global developmental delay, craniofacial dysmorphism (large fontanel, high forehead, hypertelorism, epicanthal folds) and elevated plasma very long chain fatty acids. Variable features include hepatomegaly, polymicrogyria, and cerebral white matter abnormalities, among others.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-300/","orphanet_url":"https://www.orpha.net/en/disease/detail/300","names":{"fr":{"name":"Déficit en enzyme bifonctionnelle","definition":"Anomalie rare de la bêta-oxydation péroxysomale caractérisée par un déficit en l'enzyme (protéine D-bifonctionnelle), le type 1 étant causé par un déficit de l'activité déshydrogénase et hydratase, et les types 2 et 3 par un déficit de l'activité déshydrogénase ou hydratase, tandis que le type 4 est dû à des mutations hétérozygotes composites affectant les deux sous-unités et représente un phénotype cliniquement plus léger. Les types 1 à 3 sont généralement létaux dans la petite enfance. Les patients présentent une hypotonie généralisée précoce, des crises convulsives, un retard de développement global sévère, une dysmorphie craniofaciale (large fontanelle, front haut, hypertélorisme, plis épicanthaux) et un taux élevé d'acides gras à très longue chaîne dans le plasma. Parmi les signes inconstants figurent, entre autres, l'hépatomégalie, la polymicrogyrie et les anomalies de la substance blanche cérébrale."},"de":{"name":"D-bifunktionales Enzym-Mangel","definition":"Eine seltene peroxisomale Beta-Oxidationsstörung, die durch einen Mangel des peroxisomalen D-bifunktionellen Proteins gekennzeichnet ist, wobei Typ 1 durch einen Mangel sowohl der Dehydrogenase- als auch der Hydratase-Aktivität des Enzyms verursacht wird und die Typen 2 und 3 durch einen alleinigen Hydratase- oder Dehydrogenase-Mangel, während Typ 4 auf compound-heterozygote Mutationen zurückzuführen ist, die beide Einheiten betreffen und in einem klinisch milderen Phänotyp münden. Die Typen 1-3 verlaufen in der Regel im Säuglingsalter tödlich. Die Patienten weisen eine früh einsetzende generalisierte Hypotonie, Krampfanfälle, eine schwere globale Entwicklungsverzögerung, kraniofaziale Dysmorphien (große Fontanelle, hohe Stirn, Hypertelorismus, Epikanthusfalten) und erhöhte sehr langkettige Plasmafettsäuren auf. Zu den variablen Merkmalen gehören u. a. Hepatomegalie, Polymikrogyrie und Anomalien der weißen Hirnsubstanz."},"es":{"name":"Deficiencia de enzima bifuncional","definition":"Es un trastorno poco frecuente de la beta-oxidación peroxisomal caracterizado por la deficiencia de la proteína D-bifuncional peroxisomal. El tipo 1 está causado por la deficiencia de las actividades deshidrogenasa e hidratasa de la enzima, mientras que los tipos 2 y 3 son el resultado de la deficiencia de hidratasas o deshidrogenasas únicamente, y el tipo 4 se debe a mutaciones en heterocigosis compuesta que afectan a ambas unidades y representa un fenotipo clínicamente más leve. Los tipos 1-3 suelen ser mortales en la infancia. Los pacientes se presentan a una temprana edad con hipotonía generalizada, crisis, retraso grave del desarrollo global, dismorfia craneofacial (fontanela amplia, frente alta, hipertelorismo, pliegues epicánticos) y elevación de los ácidos grasos de cadena muy larga en plasma. Otras características variables incluyen hepatomegalia, polimicrogiria y anomalías de la sustancia blanca cerebral, entre otras."},"it":{"name":"Deficit dell'enzima bifunzionale","definition":"Si tratta di un'anomalia rara della beta-ossidazione perossisomiale, caratterizzata da un deficit della proteina D-bifunzionale perossisomiale; il tipo 1 è causato dal deficit di entrambe le attività deidrogenasi e idratasi dell'enzima, i tipi 2 e 3 sono caratterizzati dalla carenza della sola idratasi o deidrogenasi, mentre il tipo 4 è causato dalle mutazioni eterozigoti composte che interessano entrambe le unità e si associano ad un fenotipo più lieve. In genere i tipi 1-3 sono letali durante l'infanzia. I pazienti presentano ipotonia generalizzata ad esordio precoce, crisi epilettiche, grave ritardo dello sviluppo globale, dismorfismi craniofacciali (fontanella ampia, fronte alta, ipertelorismo, epicanto) e livelli elevati degli acidi grassi a catena molto lunga nel plasma. I pazienti possono presentare anche epatomegalia, polimicrogiria e anomalie della sostanza bianca cerebrale."},"nl":{"name":"Deficiëntie van bifunctioneel enzym","definition":"Een zeldzame aandoening van peroxisomale bèta-oxidatie, gekarakteriseerd door deficiëntie van peroxisomaal D-bifunctioneel proteïne, waarbij type 1 wordt veroorzaakt door deficiëntie van zowel de dehydrogenase als de hydratase activiteit van het enzym, en type 2 en 3 respectievelijk door deficiëntie van enkel hydratase en dehydrogenase, terwijl type 4 een klinisch milder fenotype vertegenwoordigt dat te wijten is aan samengesteld heterozygote mutaties die beide eenheden aantasten. Types 1-3 zijn doorgaans fataal in de zuigelingentijd. Patiënten vertonen vroege aanvang van gegeneraliseerde hypotonie, insulten, ernstige algehele ontwikkelingsachterstand, craniofaciale dysmorfie (groot fontanel, hoog voorhoofd, hypertelorisme, epicanthusplooien), en verhoogde gehaltes van zeer lange keten vetzuren in plasma. Variabele kenmerken zijn onder meer hepatomegalie, polymicrogyrie, en afwijkingen van cerebrale witte stof."},"pt":{"name":"Deficiência de enzima bifuncional"},"pl":{"name":"Niedobór enzymu dwufunkcyjnego"},"cs":{"name":"Deficit bifunkčních enzymů"},"uk":{"name":"Дефіцит біфункціонального ферменту","definition":"A rare peroxisomal beta-oxidation disorder characterized by deficiency of peroxisomal D-bifunctional protein, type 1 being caused by deficiency of both dehydrogenase and hydratase activities of the enzyme, and types 2 and 3 by hydratase or dehydrogenase deficiency alone, while type 4 is due to compound heterozygous mutations affecting both units and represents a clinically milder phenotype. Types 1-3 are typically fatal in infancy. Patients present with early onset of generalized hypotonia, seizures, severe global developmental delay, craniofacial dysmorphism (large fontanel, high forehead, hypertelorism, epicanthal folds) and elevated plasma very long chain fatty acids. Variable features include hepatomegaly, polymicrogyria, and cerebral white matter abnormalities, among others."},"zh":{"name":"双功能酶缺乏"},"tr":{"name":"Bifonksiyonel enzim eksikliği"}},"xrefs":[{"source":"OMIM","code":"261515","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E71.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C57.1","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"996981847"},{"source":"MONDO","code":"0009855","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0342870","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"4539","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":2981,"name":"Pseudo-Zellweger syndrome","status":"inactive"}],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":79188,"name":"Peroxisomal beta-oxidation disorder","classifications":[150,156,233]}],"children":[],"genes":[{"symbol":"EHHADH","name":"enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"9501266[PMID]","hgnc":"3247","ensembl":"ENSG00000113790","omim":"607037","loci":["3q27.2"]},{"symbol":"HSD17B4","name":"hydroxysteroid 17-beta dehydrogenase 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"9915948[PMID]_24553428[PMID]_25967389[PMID]","hgnc":"5213","ensembl":"ENSG00000133835","omim":"601860","loci":["5q23.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"type":"Point prevalence","qualification":"Value and class","class":"<1 / 1 000 000","value":0.02,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":null}