{"orpha":254875,"name":"TK2-related mitochondrial DNA maintenance defect, myopathic form","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["TK2 deficiency","Thymidine kinase 2 deficiency","TK2d"],"definition":"A rare mitochondrial DNA depletion syndrome characterized by muscle weakness, and progressive, generalized hypotonia due to depletion of mtDNA in skeletal muscles. Clinical progression ranges from rapid and early fatal course due to respiratory failure, to slowly progressive myopathy over the course of childhood or even early adulthood.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-254875/","orphanet_url":"https://www.orpha.net/en/disease/detail/254875","names":{"fr":{"name":"Défaut de maintenance de l'ADN mitochondrial associé à TK2, forme myopathique","synonyms":["Déficit en TK2","TK2d","Déficit en thymidine kinase 2"],"definition":"Syndrome rare de déplétion de l'ADN mitochondrial caractérisé par une faiblesse musculaire et une hypotonie progressive et généralisée dues à la déplétion de l'ADNmt dans les muscles squelettiques. Sur le plan clinique, la maladie oscille entre une évolution rapide et précocement fatale due à une insuffisance respiratoire, et une myopathie lentement progressive dans l'enfance, voire au début de l'âge adulte."},"de":{"name":"TK2-assoziiertes mitochondriales DNA-Depletionssyndrom, myopathische Form","synonyms":["Thymidinkinase-2-Defizienz","TK2-Mangel"],"definition":"Ein seltenes mitochondriales DNA-Depletionssyndrom, das durch Muskelschwäche und fortschreitende, generalisierte Hypotonie aufgrund einer Depletion der mtDNA in den Skelettmuskeln gekennzeichnet ist. Der klinische Verlauf reicht von einem schnellen und frühzeitigen tödlichen Verlauf aufgrund von Atemversagen bis hin zu einer langsam fortschreitenden Myopathie im Laufe der Kindheit oder sogar im frühen Erwachsenenalter."},"es":{"name":"Defectos de mantenimiento del ADN mitocondrial asociados al gen TK2, forma miopática","synonyms":["Deficiencia de timidina quinasa 2","TK2d","Deficiencia de TK2"],"definition":"Es un síndrome poco frecuente de depleción del ADN mitocondrial caracterizado por debilidad muscular e hipotonía progresiva y generalizada debido a la depleción del ADNmt en el músculo esquelético. La progresión clínica varía desde un curso rápido y fatal precoz debido a la insuficiencia respiratoria hasta una miopatía de progresión lenta en el transcurso de la infancia o incluso en la edad adulta temprana."},"it":{"name":"Difetto del mantenimento del DNA mitocondriale correlato a TK2, forma miopatica","synonyms":["Deficit di TK2","Deficit di timidina chinasi 2","TK2d"],"definition":"La forma miopatica della sindrome da deplezione del DNA mitocondriale (mtDNA) è uno dei tipi principali della sindrome da deplezione del mtDNA (si veda questo termine). Il quadro clinico è ampio, ma in genere è caratterizzato da ipotonia, debolezza dei muscoli prossimali, debolezza facciale e bulbare e ritardo dello sviluppo."},"nl":{"name":"TK2-gerelateerd mitochondriaal DNA-handhavingsdefect, myopathische vorm","synonyms":["TK2d","TK2-deficiëntie","Deficiëntie van thymidinekinase 2"],"definition":"Een zeldzaam mitochondriaal DNA-depletiesyndroom, gekenmerkt door spierzwakte en progressieve, gegeneraliseerde hypotonie door depletie van mtDNA in skeletspier. Klinische progressie gaat van een snel en al vroeg fataal verloop als gevolg van respiratoir falen, tot traag progressieve myopathie in de loop van de kindertijd of zelfs vroege volwassenheid."},"pt":{"name":"Síndrome de depleção do ADN mitocondrial, forma miopática","synonyms":["Síndrome de depleção do ADNmt, forma miopática"],"definition":"Síndrome rara de depleção do ADN mitocondrial caracterizada por fraqueza muscular e hipotonia progressiva e generalizada devido à depleção de ADNmt nos músculos esqueléticos. A progressão clínica varia desde uma evolução rápida e fatal precoce devido a insuficiência respiratória até uma miopatia lentamente progressiva ao longo da infância ou mesmo do início da idade adulta."},"pl":{"name":"Zespół deplecji mitochondrialnego DNA, postać miopatyczna","synonyms":["Zespół deplecji mtDNA, postać miopatyczna"],"definition":"Rzadki zespół deplecji mitochondrialnego DNA charakteryzujący się osłabieniem mięśni i postępującą, uogólnioną hipotonią wynikającą z deplecji mtDNA w mięśniach szkieletowych. Klinicznie choroba może mieć szybki i wczesny przebieg, prowadzący z śmierci z powodu niewydolności oddechowej lub przejawiać się wolno postępującą miopatią w okresie dzieciństwa lub nawet wczesnej dorosłości."},"cs":{"name":"Syndrom deplece mitochondriální DNA, myopatická forma","synonyms":["Syndrom deplece mtDNA, myopatická forma"]},"uk":{"name":"Синдром виснаження мітохондріальної ДНК, міопатична форма","synonyms":["Синдром виснаження мтДНК, міопатична форма"],"definition":"A rare mitochondrial DNA depletion syndrome characterized by muscle weakness, and progressive, generalized hypotonia due to depletion of mtDNA in skeletal muscles. Clinical progression ranges from rapid and early fatal course due to respiratory failure, to slowly progressive myopathy over the course of childhood or even early adulthood."},"zh":{"name":"肌病型线粒体DNA缺失综合征","synonyms":["线粒体DNA缺失综合征肌病型"],"definition":"肌病线粒体DNA(MtDNA)耗竭综合征是mtDNA耗竭综合征(见本词条)的主要形式之一，具有广泛的表型谱，但最常见的特征是肌张力低下、近端肌肉无力、面部和延髓无力以及生长迟缓。"},"tr":{"name":"Mitokondriyal DNA tükenme sendromu, miyopatik form","synonyms":["mtDNA tükenme sendromu, miyopatik form"]}},"xrefs":[{"source":"OMIM","code":"609560","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G71.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.20","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"294556832"},{"source":"MONDO","code":"0012301","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C563698","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C3501891","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79193,"name":"Disorder of pyrimidine metabolism","classifications":[150,156]},{"orpha":35698,"name":"Mitochondrial DNA depletion syndrome","classifications":[150,156]},{"orpha":206966,"name":"Mitochondrial myopathy","classifications":[156,181]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]}],"children":[{"orpha":730743,"name":"Childhood-onset TK2-related mitochondrial DNA maintenance defect, myopathic form","type":"Clinical subtype"},{"orpha":730740,"name":"Infantile-onset TK2-related mitochondrial DNA maintenance defect, myopathic form","type":"Clinical subtype"},{"orpha":730746,"name":"Late-onset TK2-related mitochondrial DNA maintenance defect, myopathic form","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"TK2","name":"thymidine kinase 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23230576[PMID]","hgnc":"11831","ensembl":"ENSG00000166548","omim":"188250","loci":["16q21"],"via":{"orpha":730740,"name":"Infantile-onset TK2-related mitochondrial DNA maintenance defect, myopathic form"}},{"symbol":"TK2","name":"thymidine kinase 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23230576[PMID]","hgnc":"11831","ensembl":"ENSG00000166548","omim":"188250","loci":["16q21"],"via":{"orpha":730743,"name":"Childhood-onset TK2-related mitochondrial DNA maintenance defect, myopathic form"}},{"symbol":"TK2","name":"thymidine kinase 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23230576[PMID]","hgnc":"11831","ensembl":"ENSG00000166548","omim":"188250","loci":["16q21"],"via":{"orpha":730746,"name":"Late-onset TK2-related mitochondrial DNA maintenance defect, myopathic form"}}],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":45.0,"area":"Worldwide","status":"Validated","source":"23230576[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_23230576[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2024-07-09","source":"23230576[PMID]_29735374[PMID]_23932787[PMID]_23968935[PMID]","terms":[{"hpo":"HP:0003198","label":"Myopathy","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002333","label":"Motor deterioration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012432","label":"Chronic fatigue","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003698","label":"Difficulty standing","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002460","label":"Distal muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003546","label":"Exercise intolerance","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:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003324","label":"Generalized muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002197","label":"Generalized-onset seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007105","label":"Infantile encephalopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009073","label":"Progressive proximal muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006532","label":"Recurrent pneumonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002098","label":"Respiratory distress","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002747","label":"Respiratory insufficiency due to muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001488","label":"Bilateral ptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001283","label":"Bulbar palsy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008610","label":"Infantile sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003326","label":"Myalgia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000597","label":"Ophthalmoparesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000590","label":"Progressive external ophthalmoplegia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008625","label":"Severe sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005946","label":"Ventilator dependence with inability to wean","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030319","label":"Weakness of facial musculature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0007269","label":"Spinal muscular atrophy","frequency":"Very rare (<4-1%)","criteria":null}]}}