{"orpha":314051,"name":"Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["COXPD12","Combined oxidative phosphorylation defect type 12","LTBL"],"definition":"A rare, genetic neurological disorder defined by early-onset of neurologic symptoms, biphasic clinical course, unique MRI features (incl. extensive, symmetrical, deep white matter abnormalities), and increased lactate in body fluids. The severe form is characterized by delayed psychomotor development, seizures, early-onset hypotonia, and persistently increased lactate levels. The mild form usually presents with irritability, psychomotor regression after six months of age, and temporary high lactate levels, with overall clinical improvement from the second year onward.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-314051/","orphanet_url":"https://www.orpha.net/en/disease/detail/314051","names":{"fr":{"name":"Syndrome de leucoencéphalopathie-anomalies du thalamus et du tronc cérébral-hyperlactatémie","synonyms":["COXPD12","Déficit combiné de la phosphorylation oxydative type 12","LTBL"],"definition":"Trouble génétique neurologique rare caractérisé par l'apparition précoce de signes neurologiques, par une évolution clinique en deux phases, par des caractéristiques uniques à l'imagerie par résonance magnétique (IRM ; incluant des anomalies étendues et symétriques de la substance blanche profonde), et par une augmentation du lactate dans les fluides corporels. La forme sévère se caractérise par un retard du développement psychomoteur, des convulsions, une hypotonie précoce et une augmentation persistante des taux de lactate. La forme légère se manifeste par une irritabilité, une régression psychomotrice après l'âge de six mois, et une élévation temporaire des taux de lactate, associées à une amélioration clinique générale à partir de l'âge de deux ans."},"de":{"name":"Leukoenzephalopathie-Thalamus und Hirnstamm-Anomalien-Hoher Laktatwert-Syndrom","synonyms":["COXPD12","Kombinierter Defekt der oxidativen Phosphorylierung Typ 12","LTBL"],"definition":"Eine seltene, genetisch bedingte neurologische Störung, die durch ein frühes Auftreten neurologischer Symptome, einen biphasischen klinischen Verlauf, spezifische MRT-Merkmale (u. a. ausgedehnte, symmetrische, tiefe Anomalien der weißen Substanz) und erhöhte Laktatwerte in Körperflüssigkeiten definiert ist. Die schwere Form ist gekennzeichnet durch verzögerte psychomotorische Entwicklung, Krampfanfälle, früh einsetzende Hypotonie und anhaltend erhöhte Laktatwerte. Die milde Form zeigt sich in der Regel mit Reizbarkeit, psychomotorischer Regression nach dem sechsten Lebensmonat und vorübergehend hohen Laktatwerten, mit einer allgemeinen klinischen Verbesserung ab dem zweiten Lebensjahr."},"es":{"name":"Síndrome de leucoencefalopatía-anomalías del tálamo y tallo cerebral-lactato elevado","synonyms":["COXPD12","Deficiencia combinada de la fosforilación oxidativa tipo 12","LTBL"],"definition":"Es un trastorno neurológico poco frecuente de origen genético caracterizado por síntomas neurológicos de inicio temprano, curso clínico bifásico, características únicas de RM (incluyendo anomalías extensas y simétricas de la sustancia blanca profunda) y un aumento de los niveles de lactato en los fluidos corporales. La forma grave se caracteriza por retraso en el desarrollo psicomotor, crisis, hipotonía de inicio temprano y niveles de lactato persistentemente elevados. La forma leve generalmente se presenta con irritabilidad, regresión psicomotora después de los seis meses de edad y niveles de lactato temporalmente elevados, con mejoría clínica generalizada a partir del segundo año."},"it":{"name":"Sindrome leucoencefalopatia-anomalie del talamo e del tronco encefalico-livelli elevati di lattato","synonyms":["COXPD12","Difetto combinato della fosforilazione ossidativa, tipo 12","LTBL"],"definition":"La sindrome da leucoencefalopatia con anomalie del talamo e del tronco encefalico e livelli elevati di lattato (LTBL) è una malattia genetica rara, caratterizzata da segni neurologici ad esordio precoce, decorso clinico bifasico, alterazioni peculiari alla RMN (anomalie estese e simmetriche della sostanza bianca profonda) e aumento dei livelli di lattato nei liquidi del corpo. La forma grave è caratterizzata da ritardo dello sviluppo psicomotorio, crisi epilettiche, ipotonia ad esordio precoce e costante aumento dei livelli di lattato. La forma lieve di solito esordisce con irritabilità, regressione psicomotoria dopo i sei mesi di vita, livelli di lattato temporaneamente elevati e miglioramento clinico complessivo a partire dal secondo anno di vita."},"nl":{"name":"Leuko-encefalopathie - anomalieën van thalamus en hersenstam - hoog lactaatgehalte-syndroom","synonyms":["COXPD12","Gecombineerde oxidatieve fosforylatiedeficiëntie type 12","Gecombineerde oxidatieve fosforyleringdeficiëntie type 12","LTBL"],"definition":"Een zeldzame, genetische neurologische aandoening, gedefinieerd door vroeg optreden van neurologische symptomen, bifasisch klinisch verloop, unieke MRI-kenmerken (waaronder uitgebreide, symmetrische afwijkingen van diepe witte stof), en verhoogde lactaatgehaltes in lichaamsvloeistoffen. De ernstige vorm wordt gekenmerkt door psychomotorische ontwikkelingsachterstand, insulten, vroeg optredende hypotonie, en aanhoudend verhoogde lactaatgehaltes. De milde vorm presenteert zich meestal met prikkelbaarheid, psychomotorische regressie na de leeftijd van zes maanden, en tijdelijk verhoogde lactaatgehaltes, en vertoont algehele klinische verbetering vanaf de leeftijd van twee jaar."},"pt":{"name":"Leucoencefalopatia - anomalias do tronco cerebral e talamus - lactato elevado","synonyms":["LTBL"]},"pl":{"name":"Zespół leukoencefalopatii, wad podwzgórza i pnia mózgu i wysokiego poziomu mleczanów","synonyms":["LTBL","COXPD12","Złożony defekt fosforylacji oksydacyjnej typu 12"]},"cs":{"name":"Syndrom zahrnující leukoencefalopatii, anomálie thalamu a mozkového kmene a vysokou hladinu laktátu","synonyms":["COXPD12","Kombinovaný deficit oxidativní fosforylace, typ 12","LTBL"]},"uk":{"name":"Синдром лейкоенцефалопатії-аномалій таламуса та стовбура мозк-підвищеного лактату","synonyms":["Комбінований дефект окисного фосфорилювання, тип 12","COXPD12","LTBL"],"definition":"A rare, genetic neurological disorder defined by early-onset of neurologic symptoms, biphasic clinical course, unique MRI features (incl. extensive, symmetrical, deep white matter abnormalities), and increased lactate in body fluids. The severe form is characterized by delayed psychomotor development, seizures, early-onset hypotonia, and persistently increased lactate levels. The mild form usually presents with irritability, psychomotor regression after six months of age, and temporary high lactate levels, with overall clinical improvement from the second year onward."},"zh":{"name":"脑白质病-丘脑脑干异常-高乳酸综合征","synonyms":["联合氧化磷酸化缺陷12型"],"definition":"脑白质病-丘脑和脑干异常-高乳酸（LTBL）综合征是一种罕见的遗传性神经系统疾病，其特征是早期出现神经系统症状、双相临床病程、独特的MRI影像特征（包括广泛、对称、深部的白质异常）和体液中乳酸的增加。严重型的特征是精神运动发育迟缓、癫痫发作、早发性低血压和乳酸水平持续升高。轻型通常表现为易怒，六月龄后精神运动功能衰退，乳酸水平暂时升高，从第二年开始临床症状总体改善。"},"tr":{"name":"Lökoensefalopati-talamus ve beyin sapı anomalileri-yüksek laktat sendromu","synonyms":["LTBL","COXPD12","Kombine oksidatif fosforilasyon defekti tip 12"]}},"xrefs":[{"source":"OMIM","code":"614924","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E88.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.23","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0013971","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4706421","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"12893","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":68356,"name":"Leukodystrophy","classifications":[156,181]},{"orpha":35696,"name":"Mitochondrial disorder due to a defect in mitochondrial protein synthesis","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]}],"children":[],"genes":[{"symbol":"EARS2","name":"glutamyl-tRNA synthetase 2, mitochondrial","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22492562[PMID]_24501781[PMID]","hgnc":"29419","ensembl":"ENSG00000103356","omim":"612799","loci":["16p12.2"]}],"genes_via_subtypes":[],"inheritance":["No data available"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":14.0,"area":"Worldwide","status":"Validated","source":"22492562[PMID]_23008233[PMID]_25854774[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_22492562[PMID]_23008233[PMID]_25854774[PMID]"}],"phenotypes":null}