{"orpha":24,"name":"Fumaric aciduria","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Fumarase deficiency"],"definition":"Fumaric aciduria (FA), an autosomal recessive metabolic disorder, is most often characterized by early onset but non-specific clinical signs: hypotonia, severe psychomotor impairment, convulsions, respiratory distress, feeding difficulties and frequent cerebral malformations, along with a distinctive facies. Some patients present with only moderate intellectual impairment.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-24/","orphanet_url":"https://www.orpha.net/en/disease/detail/24","names":{"fr":{"name":"Acidurie fumarique","synonyms":["Déficit en fumarase"],"definition":"L'acidurie fumarique est un trouble métabolique autosomique récessif, le plus souvent caractérisé par une présentation clinique précoce non spécifique : une hypotonie, un retard psychomoteur sévère, des convulsions, une détresse respiratoire, des difficultés pour s'alimenter, des malformations cérébrales fréquentes et une dysmorphie faciale. Certains patients présentent uniquement un déficit intellectuel modéré."},"de":{"name":"Fumarazidurie","synonyms":["Fumarase-Mangel"],"definition":"Die Fumarazidurie (FA), eine autosomal-rezessiv vererbte Stoffwechselstörung, ist in den meisten Fällen durch frühen Beginn und unspezifische klinische Symptome gekennzeichnet: Muskelhypotonie, schwere psychomotorische Beeinträchtigung, Krämpfe, Ateminsuffizienz, Probleme bei der Nahrungsaufnahme, häufige Hirnfehlbildungen und eine charakteristische Fazies. Einige Patienten weisen eine nur leichte geistige Beeinträchtigung auf."},"es":{"name":"Aciduria fumárica","synonyms":["Deficiencia de fumarasa"],"definition":"La aciduria fumárica (FA) es un trastorno autosómico recesivo del metabolismo que se caracteriza habitualmente por una aparición temprana pero sin signos clínicos específicos: hipotonía, deterioro psicomotor grave, convulsiones, dificultades respiratorias, en la alimentación y frecuentes malformaciones cerebrales, junto con facies peculiar. Algunos pacientes presentan sólo un déficit intelectual moderado."},"it":{"name":"Aciduria fumarica","synonyms":["Deficit di fumarasi"],"definition":"L'aciduria fumarica (FA), una patologia metabolica autosomica recessiva, è caratterizzata spesso da segni clinici ad esordio precoce ma non specifici: ipotonia, deficit psicomotorio grave, convulsioni, distress respiratorio, difficoltà alimentari, malformazioni cerebrali comuni e facies caratteristica. Alcuni pazienti presentano esclusivamente deficit cognitivo moderato."},"nl":{"name":"Fumarasedeficiëntie","synonyms":["Fumaarzuuracidurie"],"definition":"Fumaarzuuracidurie (FA), een autosomaal recessieve stofwisselingsziekte, wordt meestal gekenmerkt door een vroege aanvang, maar veroorzaakt niet-specifieke klinische symptomen: hypotonie, ernstige psychomotorische stoornis, convulsies, ademnood, voedingsproblemen en frequente cerebrale misvormingen, samen met een distinctief aangezicht. Sommige patiënten presenteren zich met slechts een matige intellectuele beperking."},"pt":{"name":"Acidúria fumárica","synonyms":["Deficiência de fumarase"]},"pl":{"name":"Acyduria fumarowa","synonyms":["Niedobór fumarazy"]},"cs":{"name":"Fumarová acidurie","synonyms":["Deficit fumarázy"]},"uk":{"name":"Фумарова ацидурія","synonyms":["Дефіцит фумарази"],"definition":"Fumaric aciduria (FA), an autosomal recessive metabolic disorder, is most often characterized by early onset but non-specific clinical signs: hypotonia, severe psychomotor impairment, convulsions, respiratory distress, feeding difficulties and frequent cerebral malformations, along with a distinctive facies. Some patients present with only moderate intellectual impairment."},"zh":{"name":"富马酸尿症","synonyms":["延胡索酸酶缺乏症"]},"tr":{"name":"Fumarik asidüri","synonyms":["Fumaraz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"606812","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E88.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.1","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"780506966"},{"source":"MONDO","code":"0011730","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C538191","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0342770","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"6476","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10088204","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":225700,"name":"Mitochondrial disease with epilepsy","classifications":[156,181]},{"orpha":225703,"name":"Mitochondrial disease with peripheral neuropathy","classifications":[156,181]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":254749,"name":"Tricarboxylic acid cycle disorder","classifications":[150,156]}],"children":[],"genes":[{"symbol":"FH","name":"fumarate hydratase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301679[PMID]","hgnc":"3700","ensembl":"ENSG00000091483","omim":"136850","loci":["1q43"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":40.0,"area":"Worldwide","status":"Validated","source":"22069215[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_22069215[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2025-06-05","source":"20301679[PMID]_33052056[PMID]","terms":[{"hpo":"HP:0003536","label":"Decreased fumarate hydratase activity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001531","label":"Failure to thrive in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002007","label":"Frontal bossing","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001622","label":"Premature birth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002500","label":"Abnormal cerebral white matter morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001273","label":"Abnormal corpus callosum morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025646","label":"Bilateral polymicrogyria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006808","label":"Cerebral hypomyelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003191","label":"Cleft ala nasi","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001259","label":"Coma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001875","label":"Decreased total neutrophil count","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0034648","label":"Elevated urine fumaric acid level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002521","label":"Hypsarrhythmia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012402","label":"Increased urine alpha-ketoglutarate concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001562","label":"Oligohydramnios","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001901","label":"Polycythemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000817","label":"Reduced eye contact","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010804","label":"Tented upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001987","label":"Hyperammonemia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001942","label":"Metabolic acidosis","frequency":"Very rare (<4-1%)","criteria":null}]}}