{"orpha":480864,"name":"Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["TANGO2-related metabolic encephalopathy-arrhythmia syndrome"],"definition":"Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome is a rare, genetic, neurodegenerative disease characterized by episodic metabolic encephalomyopathic crises (of variable frequency and severity which are frequently precipitated by an acute illness) which manifest with profound muscle weakness, ataxia, seizures, cardiac arrhythmias, rhabdomyolysis with myoglobinuria, elevated plasma creatine kinase, hypoglycemia, lactic acidosis, increased acylcarnitines and a disorientated or comatose state. Global developmental delay, intellectual disability and cortical, pyramidal and cerebellar signs develop with subsequent progressive neurodegeneration causing loss of expressive language and varying degrees of cerebral atrophy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-480864/","orphanet_url":"https://www.orpha.net/en/disease/detail/480864","names":{"fr":{"name":"Syndrome de crises encéphalomyopathiques métaboliques récurrentes-rhabdomyolyse-arythmie cardiaque-déficience intellectuelle","synonyms":["Syndrome d'encéphalopathie métabolique-arythmie associé à TANGO2"],"definition":"Une maladie génétique neurodégénérative rare caractérisée par des crises encéphalomyopathiques métaboliques épisodiques (de fréquence et de sévérité variable, et souvent précipitées par une maladie aigüe), qui se manifestent par une faiblesse musculaire sévère, une ataxie, des convulsions des arythmies cardiaques, une rhabdomyolyse avec myoglobinurie, un taux élevé en créatine kinase plasmatique, une hypoglycémie, une acidose lactique, un taux élevé d'acylcarnitine et une désorientation ou un état comateux. Un retard du développement global, un déficit intellectuel et des signes corticaux, pyramidaux et cérébelleux se développent, avec pour conséquence une neuro-dégénérescence progressive responsable d'une perte du langage expressif et une atrophie cérébrale de sévérité variable."},"de":{"name":"Rezidivierende metabolische enzephalomyopathische Krisen-Rhabdomyolyse-Herzrhythmusstörung-Intelligenzminderung-Syndrom","synonyms":["TANGO2-assoziierte metabolische Enzephalopathie-Arrhythmie-Syndrom"],"definition":"Eine seltene, genetisch bedingte neurodegenerative Erkrankung, die durch episodische metabolische enzephalomyopathische Krisen von unterschiedlicher Häufigkeit und Schwere (häufig durch eine akute Erkrankung ausgelöst) gekennzeichnet ist. Sie manifestiert sich mit ausgeprägter Muskelschwäche, Ataxie, Krampfanfällen, Herzrhythmusstörungen, Rhabdomyolyse mit Myoglobinurie, erhöhter Plasma-Kreatinkinase, Hypoglykämie, Laktatazidose, erhöhten Acylcarnitinen und einem desorientierten oder komatösen Zustand. Es entwickeln sich eine allgemeine Entwicklungsverzögerung, Intelligenzminderung und kortikale, pyramidale und zerebelläre Anzeichen mit anschließender progressiver Neurodegeneration, die zu einer Störung der expressiven Sprache und unterschiedlichen Graden der zerebralen Atrophie führt."},"es":{"name":"Síndrome de crisis encefalomiopáticas metabólicas recurrentes-rabdomiólisis-arritmia cardíaca-discapacidad intelectual","synonyms":["Síndrome de encefalopatía metabólica-arritmia asociado a TANGO2"],"definition":"Es una enfermedad neurodegenerativa genética y poco frecuente. Está caracterizada por crisis metabólicas encefalomiopáticas episódicas agudas (de frecuencia y gravedad variables, por lo habitual desencadenadas por una enfermedad aguda), que se manifiestan con una profunda debilidad muscular, ataxia, convulsiones, arritmias cardíacas, rabdomiolisis con mioglobinuria, niveles elevados de creatinquinasa plasmática, hipoglucemia, acidosis láctica, valores aumentados de acilcarnitinas y un estado comatoso o de desorientación. El retraso global del desarrollo, discapacidad intelectual y los signos corticales, piramidales y cerebelosos se desarrollan con la subsecuente neurodegeneración progresiva, ocasionando la pérdida del lenguaje expresivo y diversos grados de atrofia cerebral."},"it":{"name":"Sindrome crisi encefalomiopatiche metaboliche ricorrenti-rabdomiolisi-aritmia cardiaca-disabilità intellettiva","synonyms":["Sindrome da encefalopatia metabolica e aritmia correlata a TANGO2"],"definition":"La sindrome da crisi encefalomiopatiche metaboliche ricorrenti, rabdomiolisi, aritmia cardiaca e disabilità intellettiva è una malattia neurodegenerativa genetica rara, caratterizzata da episodi di crisi encefalomiopatiche metaboliche (di frequenza e gravità variabile, spesso scatenate da una malattia acuta) che esordiscono con debolezza muscolare marcata, atassia, crisi epilettiche, aritmie cardiache, rabdomiolisi con mioglobinuria, livelli elevati di creatin-chinasi nel plasma, ipoglicemia, acidosi lattica, livelli elevati di acilcarnitine e disorientamento o stato comatoso. I pazienti presentano ritardo dello sviluppo, disabilità intellettiva e segni corticali, piramidali e cerebellari, associati a degenerazione neurologica progressiva, che esita nella perdita del linguaggio espressivo e nell'atrofia cerebrale di grado variabile."},"nl":{"name":"Recidiverende metabole encefalomyopathische crises - rhabdomyolyse - hartritmestoornis - intellectuele achterstand-syndroom","synonyms":["TANGO2-gerelateerd metabole encefalopathie - aritmie-syndroom"],"definition":"Recurrente metabole encefalomyopathische crises - rhabdomyolyse - hartritmestoornis - intellectuele achterstand-syndroom is een zeldzame, genetische, neurodegeneratieve ziekte, gekarakteriseerd door episodische metabole encefalomyopathische crises (met variabele frequentie en ernst, vaak bevorderd door een acute ziekte) die zich manifesteren met ernstige spierzwakte, ataxie, insulten, hartritmestoornissen, rhabdomyolyse met myoglobinurie, verhoogd gehalte van creatinekinase in plasma, hypoglycemie, lactaatacidose, verhoogde hoeveelheid acylcarnitines, en een gedesoriënteerde of comateuze toestand. Er ontwikkelt zich algehele ontwikkelingsachterstand, intellectuele achterstand en corticale, piramidale en cerebellaire tekenen, met daaropvolgend progressieve neurodegeneratie die leidt tot expressieve taalstoornis en wisselende gradaties van cerebrale atrofie."},"pt":{"name":"Síndrome com crises encefalomiopáticas metabólicas recorrentes-rabdomiólise-arritmia cardíaca-perturbação do desenvolvimento intelectual","synonyms":["Síndrome de arritmia-encefalopatia metabólica TANGO2-relacionada"]},"pl":{"name":"Zespół nawracającego przełomu metabolicznego o charakterze encefalomiopatii, rabdomiolizy, arytmii serca i niepełnosprawności intelektualnej","synonyms":["TANGO2-related metabolic encephalopathy-arrhythmia syndrome"]},"cs":{"name":"Syndrom zahrnující opakované metabolické encefalopatické krize, rhabdomyolýzu, srdeční arytmie a mentální retardaci","synonyms":["TANGO2-related metabolic encephalopathy-arrhythmia syndrome"]},"uk":{"name":"Синдром рецидивуючих метаболічних енцефаломіопатичних кризів-рабдоміолізу-серцевої аритмії-інтелектуальної недостатності","synonyms":["Синдром метаболічної енцефалопатії-аритмії, повязаний з TANGO2"],"definition":"Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome is a rare, genetic, neurodegenerative disease characterized by episodic metabolic encephalomyopathic crises (of variable frequency and severity which are frequently precipitated by an acute illness) which manifest with profound muscle weakness, ataxia, seizures, cardiac arrhythmias, rhabdomyolysis with myoglobinuria, elevated plasma creatine kinase, hypoglycemia, lactic acidosis, increased acylcarnitines and a disorientated or comatose state. Global developmental delay, intellectual disability and cortical, pyramidal and cerebellar signs develop with subsequent progressive neurodegeneration causing loss of expressive language and varying degrees of cerebral atrophy."},"zh":{"name":"复发性代谢性脑脊髓病-横纹肌溶解症-心脏心律不齐-智力障碍综合征","synonyms":["TANGO2-related metabolic encephalopathy-arrhythmia syndrome"],"definition":"复发性代谢性脑肌病危象-横纹肌溶解-心律失常-智力障碍综合征是一种罕见遗传性的，以发作代谢性脑肌病危象（频率和严重程度不一，常由急性疾病诱发）为特征的神经退行性疾病，表现为深度肌无力。共济失调、癫痫发作、心律失常、横纹肌溶解并伴有肌红蛋白尿、血浆肌酸激酶升高、低血糖、乳酸酸中毒、酰基肉毒碱增加以及陷入迷失方向或昏迷状态。全面发育迟缓、智力障碍及皮质、锥体束和小脑体征，随后出现进行性神经变性，导致表达性语言丧失和不同程度的脑萎缩。"},"tr":{"name":"Tekrarlayan metabolik ensefalomiyopatik krizler-rabdomiyoliz-kardiyak aritmi-zihinsel yetersizlik sendromu","synonyms":["TANGO2-related metabolic encephalopathy-arrhythmia syndrome"]}},"xrefs":[{"source":"OMIM","code":"616878","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G31.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8E4Y","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0018820","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5567524","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"13423","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":101934,"name":"Genetic cardiac rhythm disease","classifications":[146,156]},{"orpha":183500,"name":"Genetic neurodegenerative disease","classifications":[156]},{"orpha":225713,"name":"Other metabolic disease with epilepsy","classifications":[156,181]},{"orpha":182070,"name":"Rare neurodegenerative disease","classifications":[181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"TANGO2","name":"transport and golgi organization 2 homolog","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"26805781[PMID]_26805782[PMID]","hgnc":"25439","ensembl":"ENSG00000183597","omim":"616830","loci":["22q11.21"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":24.0,"area":"Worldwide","status":"Validated","source":"26805781[PMID]_26805782[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26805781[PMID]_26805782[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-01-07","source":"29369572[PMID]_30245509[PMID]_31339582[PMID]_26805782[PMID]_26805781[PMID]","terms":[{"hpo":"HP:0003115","label":"Abnormal EKG","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003458","label":"EMG: myopathic abnormalities","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002919","label":"Ketonuria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002071","label":"Abnormality of extrapyramidal motor function","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008942","label":"Acute rhabdomyolysis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011675","label":"Arrhythmia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008223","label":"Compensated hypothyroidism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031936","label":"Delayed ability to walk","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002579","label":"Gastrointestinal dysmotility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002283","label":"Global brain atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001987","label":"Hyperammonemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002311","label":"Incoordination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004305","label":"Involuntary movements","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011343","label":"Moderate global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001657","label":"Prolonged QT interval","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000646","label":"Amblyopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002169","label":"Clonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0045045","label":"Elevated plasma acylcarnitine levels","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002384","label":"Focal impaired awareness seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002123","label":"Generalized myoclonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010818","label":"Generalized tonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002173","label":"Hypoglycemic seizures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011342","label":"Mild global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031165","label":"Multifocal seizures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001297","label":"Stroke","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000605","label":"Supranuclear gaze palsy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Very rare (<4-1%)","criteria":null}]}}