{"orpha":572798,"name":"WARS2-related combined oxidative phosphorylation defect","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Mitochondrial tryptophanyl-tRNA synthetase deficiency"],"definition":"A rare mitochondrial oxidative phosphorylation disorder characterized by a spectrum of three main clinical phenotypes comprising a severe neonatal phenotype with early fatal lactic acidosis, a more protracted course with early-onset developmental delay, motor weakness, extrapyramidal signs, and with or without epilepsy, and a phenotype with normal early development and Parkinson-like symptoms starting around the age of one year. Additional, variably reported, signs and symptoms include cardiomyopathy, optic anomalies, hepatosplenomegaly, and abnormal brain MRI findings, among others. Deficiencies in mitochondrial oxidative phosphorylation enzymes are inconsistent.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-572798/","orphanet_url":"https://www.orpha.net/en/disease/detail/572798","names":{"fr":{"name":"Déficit combiné de la phosphorylation oxydative associé à WARS2","synonyms":["Déficit en tryptophanyl-ARNt synthétase mitochondriale"],"definition":"Anomalie rare de la phosphorylation oxydative mitochondriale caractérisée par un spectre de trois phénotypes cliniques principaux associant un phénotype néonatal sévère avec une acidose lactique précoce fatale, une évolution plus prolongée avec un retard de développement à début précoce, un déficit moteur, des signes d'atteinte extrapyramidale, avec ou sans épilepsie, et un phénotype avec un développement précoce normal et des symptômes de type maladie de Parkinson se manifestant vers l'âge d'un an. D'autres signes et symptômes, rapportés de manière inconstante, comprennent une cardiomyopathie, des anomalies optiques, une hépatosplénomégalie et des anomalies mises en évidence à l'IRM cérébrale, entre autres. Les anomalies impliquant des enzymes utilisées dans la phosphorylation oxydative mitochondriale sont inconstantes."},"de":{"name":"Kombinierter Defekt der oxidativen Phosphorylierung, WARS2-assoziierter","synonyms":["Mitochondriale Tryptophanyl-tRNA-Synthetase-Defizienz"],"definition":"Eine seltene mitochondriale Störung der oxidativen Phosphorylierung, die durch ein Spektrum von drei klinischen Hauptphänotypen gekennzeichnet ist: einen schweren neonatalen Phänotyp mit frühzeitiger tödlicher Laktatazidose, einen langwierigeren Verlauf mit früh einsetzender Entwicklungsverzögerung, motorischer Schwäche, extrapyramidalen Anzeichen und mit oder ohne Epilepsie sowie einen Phänotyp mit normaler Frühentwicklung und Parkinson-ähnlichen Symptomen ab dem Alter von etwa einem Jahr. Zu den weiteren, unterschiedlich berichteten Anzeichen und Symptomen gehören u. a. Kardiomyopathie, optische Anomalien, Hepatosplenomegalie und abnorme MRT-Befunde des Gehirns. Defizite bei den mitochondrialen Enzymen der oxidativen Phosphorylierung sind uneinheitlich."},"es":{"name":"Deficiencia combinada de la fosforilación oxidativa asociada a WARS2","synonyms":["Deficiencia de triptofanil-ARNt sintetasa mitocondrial"],"definition":"Es un trastorno poco frecuente de la fosforilación oxidativa mitocondrial caracterizado por un espectro de tres fenotipos clínicos principales que comprenden un fenotipo neonatal grave con acidosis láctica fatal temprana, un curso más prolongado con retraso del desarrollo de inicio precoz, debilidad motora, signos extrapiramidales con o sin epilepsia, y un fenotipo con un desarrollo temprano normal y síntomas similares a los de Parkinson que comienzan alrededor del año de edad. Los signos y síntomas adicionales, descritos de forma variable, incluyen miocardiopatía, anomalías ópticas, hepatoesplenomegalia y hallazgos anómalos en la RM cerebral, entre otros. Las deficiencias de las enzimas de fosforilación oxidativa mitocondrial son inconsistentes."},"it":{"name":"Difetto combinato della fosforilazione ossidativa correlato a WARS2","synonyms":["Deficit di triptofanil-tRNA sintetasi mitocondriale"]},"nl":{"name":"WARS2-gerelateerde gecombineerde oxidatieve fosforylatiedeficiëntie","synonyms":["Deficiëntie van mitochondriaal tryptofanyl-tRNA-synthetase"],"definition":"Een zeldzame stoornis van mitochondriale oxidatieve fosforylatie, gekenmerkt door een spectrum met drie belangrijke klinische fenotypes, zijnde een ernstig neonataal fenotype met vroege fatale lactaatacidose, een meer langdurig verloop met vroeg optredende ontwikkelingsachterstand, motorische zwakte, extrapiramidale verschijnselen, en met of zonder epilepsie, en een fenotype met normale vroege ontwikkeling en Parkinson-achtige symptomen die optreden rond de leeftijd van één jaar. Bijkomende verschijnselen en symptomen die afwisselend worden gerapporteerd, zijn onder meer cardiomyopathie, ooganomalieën, hepatosplenomegalie, en abnormale bevindingen bij MRI van hersenen. Deficiënties van enzymen van mitochondriale oxidatieve fosforylatie zijn inconsistent."},"pt":{"name":"Defeito combinado da fosforilação oxidativa WARS2-relacionado","definition":"Distúrbio raro de fosforilação oxidativa mitocondrial caracterizado por um espectro de três fenótipos clínicos principais, que engloba um fenótipo neonatal grave com acidose láctica fatal precoce, um curso da doença mais prolongado com atraso no desenvolvimento de início precoce, fraqueza motora, sinais extrapiramidais e com ou sem epilepsia, e um fenótipo com desenvolvimento inicial normal e sintomas semelhantes aos de Parkinson com início aproximadamente aos doze meses de idade. Sinais e sintomas adicionais, relatados de forma variável, incluem cardiomiopatia, anomalias ópticas, hepatoesplenomegalia e achados anómalos na ressonância magnética cerebral, entre outros. As deficiências de enzimas de fosforilação oxidativa mitocondrial são inconsistentes."},"pl":{"name":"Złożony defekt fosforylacji oksydacyjnej związany z WARS2","synonyms":["Mitochondrial tryptophanyl-tRNA synthetase deficiency"],"definition":"Rzadko występujące zaburzenie mitochondrialnej fosforylacji oksydacyjnej, charakteryzujące się spektrum trzech głównych fenotypów klinicznych, które obejmują: ciężki śmiertelny fenotyp noworodkowy z kwasicą mleczanową, fenotyp o przewlekłym przebiegu z wczesnym opóźnieniem rozwoju, osłabieniem siły mięśniowej, objawami pozapiramidowymi oraz z padaczką lub bez padaczki oraz fenotyp charakteryzujący się prawidłowym wczesnym rozwojem i objawami przypominającymi chorobę Parkinsona, rozpoczynającymi się około pierwszego roku życia. Dodatkowo opisywano objawy przedmiotowe i podmiotowe obejmują między innymi kardiomiopatię, wady narządu wzroku, hepatosplenomegalię i nieprawidłowy obraz MRI mózgu. Konkretne niedobory mitochondrialnych enzymów fosforylacji oksydacyjnej nie zostały określone."},"cs":{"name":"WARS2-vázaný kombinovaný defekt oxidativní fosforylace","synonyms":["Mitochondrial tryptophanyl-tRNA synthetase deficiency"]},"uk":{"name":"Повязаний з WARS2 комбінований дефект окисного фосфорилювання","synonyms":["Дефіцит мітохондріальної триптофаніл-тРНК-синтетази"],"definition":"A rare mitochondrial oxidative phosphorylation disorder characterized by a spectrum of three main clinical phenotypes comprising a severe neonatal phenotype with early fatal lactic acidosis, a more protracted course with early-onset developmental delay, motor weakness, extrapyramidal signs, and with or without epilepsy, and a phenotype with normal early development and Parkinson-like symptoms starting around the age of one year. Additional, variably reported, signs and symptoms include cardiomyopathy, optic anomalies, hepatosplenomegaly, and abnormal brain MRI findings, among others. Deficiencies in mitochondrial oxidative phosphorylation enzymes are inconsistent."},"zh":{"name":"WARS2相关复合氧化磷酸化缺陷","synonyms":["线粒体色氨酰-tRNA合成酶缺乏症"]},"tr":{"name":"WARS2 ile ilgili kombine oksidatif fosforilasyon defekti","synonyms":["Mitokondriyal triptofanil-tRNA sentetaz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"617710","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E88.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.2Y","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0060578","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4540192","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":35696,"name":"Mitochondrial disorder due to a defect in mitochondrial protein synthesis","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":"WARS2","name":"tryptophanyl tRNA synthetase 2, mitochondrial","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28236339[PMID]_29783990[PMID]","hgnc":"12730","ensembl":"ENSG00000116874","omim":"604733","loci":["1p12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":11.0,"area":"Worldwide","status":"Validated","source":"29783990[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_29783990[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-08-28","source":"29783990[PMID]_28236339[PMID]_28650581[PMID]_28905505[PMID]","terms":[{"hpo":"HP:0100022","label":"Abnormality of movement","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012379","label":"Abnormal enzyme/coenzyme activity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002518","label":"Abnormal periventricular white matter morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002167","label":"Abnormality of speech or vocalization","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000718","label":"Aggressive behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012430","label":"Cerebral white matter hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003700","label":"Generalized amyotrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002342","label":"Intellectual disability, moderate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002451","label":"Limb dystonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002509","label":"Limb hypertonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","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:0001999","label":"Abnormal facial shape","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000646","label":"Amblyopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002305","label":"Athetosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001638","label":"Cardiomyopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003698","label":"Difficulty standing","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002198","label":"Dilated fourth ventricle","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001310","label":"Dysmetria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000577","label":"Exotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002365","label":"Hypoplasia of the brainstem","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007772","label":"Impaired smooth pursuit","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002187","label":"Intellectual disability, profound","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006956","label":"Lateral ventricle dilatation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002352","label":"Leukoencephalopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031165","label":"Multifocal seizures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001998","label":"Neonatal hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005656","label":"Positional foot deformity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000510","label":"Rod-cone dystrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002510","label":"Spastic tetraplegia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001873","label":"Thrombocytopenia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012704","label":"Widened subarachnoid space","frequency":"Occasional (29-5%)","criteria":null}]}}