{"orpha":352447,"name":"Progressive external ophthalmoplegia-myopathy-emaciation syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Mitochondrial DNA maintenance syndrome due to MGME1 deficiency","PEO-myopathy-emaciation syndrome","mtDNA maintenance syndrome due to MGME1 deficiency"],"definition":"Progressive external ophthalmoplegia-myopathy-emaciation syndrome is a rare mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies characterized by progressive external ophthalmoplegia without diplopia, cerebellar atrophy, proximal skeletal muscle weakness with generalized muscle wasting, profound emaciation, respiratory failure, spinal deformity and facial muscle weakness (manifesting with ptosis, dysphonia, dysphagia and nasal speech). Intellectual disability, gastrointestinal symptoms (e.g. nausea, abdominal fullness, and loss of appetite), dilated cardiomyopathy and renal colic have also been reported.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-352447/","orphanet_url":"https://www.orpha.net/en/disease/detail/352447","names":{"fr":{"name":"Syndrome d'ophtalmoplégie externe progressive-myopathie-émaciation","synonyms":["Syndrome d'OEP-myopathie-émaciation","Syndrome d'OEP-myopathie-émaciement","Syndrome d'ophtalmoplégie externe progressive-myopathie-émaciement","Syndrome de maintenance de l'ADN mitochondrial par déficit en MGME1","Syndrome de maintenance de l'ADNmt par déficit en MGME1"],"definition":"Un trouble rare de la phosphorylation oxydative mitochondriale causé par des anomalies de l'ADN nucléaire. Il se caractérise par une ophtalmoplégie externe progressive sans diplopie, une atrophie cérébelleuse, une faiblesse des muscles squelettiques proximaux avec fonte musculaire généralisée, une émaciation sévère, une insuffisance respiratoire, une déformation vertébrale et une faiblesse des muscles du visage (se manifestant par un ptosis, une dysphonie, une dysphagie et une voix nasale). Un déficit intellectuel, des signes gastro-intestinaux (comme des nausées, une plénitude abdominale et une perte de l'appétit), une cardiomyopathie dilatée et une colique néphrétique ont aussi été rapportés."},"de":{"name":"Progressive externe Ophthalmoplegie-Myopathie-Kachexie-Syndrom","synonyms":["Mitochondriales DNA-Maintenance-Syndrom durch MGME1-Mangel","PEO-Myopathie-Kachexie-Syndrom","mtDNA-Maintenance-Syndrom durch MGME1-Mangel"],"definition":"Eine seltene mitochondriale oxidative Phosphorylierungsstörung, die auf nukleären DNA-Anomalien beruht und durch eine progressive externe Ophthalmoplegie ohne Diplopie, Kleinhirnatrophie, proximale Skelettmuskelschwäche mit generalisiertem Muskelschwund, starke Abmagerung, respiratorische Insuffizienz, Wirbelsäulendeformität und Schwäche der Fazialmuskeln (manifestiert mit Ptosis, Dysphonie, Dysphagie und nasalem Sprechen) gekennzeichnet ist. Es wurde auch über Intelligenzminderung, gastrointestinale Symptome (z. B. Übelkeit, Völlegefühl und Appetitlosigkeit), dilatative Kardiomyopathie und Nierenkoliken berichtet."},"es":{"name":"Síndrome de oftalmoplejía externa progresiva-miopatía-emaciación","synonyms":["PEO-miopatía-emaciación","Síndrome de mantenimiento del ADN mitocondrial por deficiencia de MGME1","Síndrome de mantenimiento del ADNmt por deficiencia de MGME1"],"definition":"El síndrome de oftalmoplejía externa progresiva - miopatía - emaciación es un trastorno de la fosfoforilación oxidativa mitocondrial poco frecuente, debido a anomalías en el ADN nuclear caracterizadas por oftalmoplejía externa progresiva sin diplopía, atrofia cerebelosa, debilidad del músculo esquelético proximal con atrofia muscular generalizada, emaciación profunda, insuficiencia respiratoria, deformidad espinal y debilidad muscular facial (que se manifiesta con ptosis, disfonía, disfagia y voz nasal). También se han notificado discapacidad intelectual, síntomas gastrointestinales (p. ej., náuseas, plenitud abdominal y pérdida de apetito), cardiomiopatía dilatada y cólico renal."},"it":{"name":"Sindrome da oftalmoplegia esterna progressiva - miopatia - emaciamento","definition":"La sindrome da oftalmoplegia esterna progressiva, con miopatia ed emaciamento è una malattia rara della fosforilazione ossidativa mitocondriale, causata da anomalie del DNA nucleare. È caratterizzata da oftalmoplegia esterna progressiva senza diplopia, atrofia cerebellare, debolezza dei muscoli scheletrici prossimali, associata ad atrofia muscolare generalizzata, grave emaciamento, insufficienza respiratoria, deformità della colonna vertebrale e debolezza dei muscoli facciali (che si manifesta con ptosi, disfonia, disfagia e voce nasale). Sono stati descritti pazienti con disabilità intellettiva, sintomi gastrointestinali (nausea, senso di pienezza addominale, perdita dell'appetito), cardiomiopatia dilatativa e coliche renali."},"nl":{"name":"Progressieve externe oftalmoplegie - myopathie - emaciatie-syndroom","synonyms":["Mitochondriaal DNA-handhavingssyndroom door MGME1-deficiëntie","PEO - myopathie - emaciatie-syndroom","mtDNA-handhavingssyndroom door MGME1-deficiëntie"],"definition":"Progressieve externe oftalmoplegie - myopathie - emaciatie-syndroom is een zeldzame stoornis van de mitochondriale oxidatieve fosforylatie als gevolg van anomalieën van het nucleair DNA, en wordt gekarakteriseerd door progressieve externe oftalmoplegie zonder diplopie, cerebellaire atrofie, zwakte van proximale skeletspieren met gegeneraliseerde spieratrofie, ernstige emaciatie, respiratoire insufficiëntie, misvorming van de wervelkolom en zwakte van de gelaatsspieren (die zich manifesteert met ptose, dysfonie, dysfagie en een nasale stem). Intellectuele achterstand, gastro-intestinale symptomen (e.g. misselijkheid, vol gevoel in de buik, en verlies van eetlust), gedilateerde cardiomyopathie en nierkolieken werden ook reeds gerapporteerd."},"pt":{"name":"Síndrome de oftalmoplegia externa progressiva-miopatia-emaciação"},"pl":{"name":"Postępująca oftalmoplegia zewnętrzna - miopatia - wyniszczenie","synonyms":["PEO - miopatia - wyniszczenie","Zespół utrzymania mitochondrialnego DNA z powodu niedoboru MGME1","Zespół utrzymania mtDNA z powodu niedoboru MGME1"]},"cs":{"name":"Syndrom zahrnující progresivní externí oftalmoplegii, myopatii a emaciaci","synonyms":["Syndrom zahrnující PEO, myopatii a emaciaci","Syndrom poruchy mitochondriální DNA, způsobený deficitem MGME1","Syndrom poruchy mtDNA způsobený deficitem MGME1"]},"uk":{"name":"Синдром прогресуючої зовнішньої офтальмоплегії-міопатії-виснаження","synonyms":["Синдром підтримки мітохондріальної ДНК через дефіцит MGME1","синдром підтримки мтДНК через дефіцит MGME1","Синдром PEO-міопатія-виснаження"],"definition":"Progressive external ophthalmoplegia-myopathy-emaciation syndrome is a rare mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies characterized by progressive external ophthalmoplegia without diplopia, cerebellar atrophy, proximal skeletal muscle weakness with generalized muscle wasting, profound emaciation, respiratory failure, spinal deformity and facial muscle weakness (manifesting with ptosis, dysphonia, dysphagia and nasal speech). Intellectual disability, gastrointestinal symptoms (e.g. nausea, abdominal fullness, and loss of appetite), dilated cardiomyopathy and renal colic have also been reported."},"zh":{"name":"进行性眼外肌麻痹-肌病-消瘦综合征","synonyms":["MGME1基因缺陷所致线粒体DNA维持综合征"],"definition":"进行性外眼肌麻痹-肌病-消瘦综合征是一种罕见的由核DNA异常引起的线粒体氧化磷酸化障碍，其特征是进行性外眼肌麻痹，无复视，小脑萎缩，近端骨骼肌无力伴全身肌肉萎缩，极度消瘦，呼吸衰竭、脊柱畸形和面部肌肉无力（表现为上睑下垂、构音困难、吞咽困难和鼻音）。智力障碍、胃肠道症状（如恶心、腹胀和食欲不振）、扩张型心肌病和肾绞痛也有报道。"},"tr":{"name":"ilerleyici eksternal oftalmopleji-miyopati-zayıflama sendromu","synonyms":["PEO-miyopati-zayıflama sendromu","MGME1 eksikliğine bağlı mtDNA bakım sendromu","MGME1 eksikliğine bağlı mitokondriyal DNA idame sendromu"]}},"xrefs":[{"source":"OMIM","code":"615084","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G71.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8C73.Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0014039","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4707098","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":352456,"name":"Mitochondrial DNA maintenance syndrome","classifications":[150,156]},{"orpha":206966,"name":"Mitochondrial myopathy","classifications":[156,181]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":522522,"name":"Rare genetic neuromuscular disorder with ocular motility/alignment anomaly","classifications":[156]},{"orpha":519347,"name":"Rare neuromuscular disorder with ocular motility/alignment anomaly","classifications":[189]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"MGME1","name":"mitochondrial genome maintenance exonuclease 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"23313956[PMID]","hgnc":"16205","ensembl":"ENSG00000125871","omim":"615076","loci":["20p11.23"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["All ages"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":6.0,"area":"Worldwide","status":"Validated","source":"23313956[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2018-12-03","source":"23313956[PMID]","terms":[{"hpo":"HP:0000590","label":"Progressive external ophthalmoplegia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0040013","label":"Decreased mitochondrial number","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001644","label":"Dilated cardiomyopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001618","label":"Dysphonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002094","label":"Dyspnea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003388","label":"Easy fatigability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003546","label":"Exercise intolerance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003700","label":"Generalized amyotrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001611","label":"Hypernasal speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002808","label":"Kyphosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003198","label":"Myopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002018","label":"Nausea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003200","label":"Ragged-red muscle fibers","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002719","label":"Recurrent infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008443","label":"Spinal deformities","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003306","label":"Spinal rigidity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030319","label":"Weakness of facial musculature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000787","label":"Nephrolithiasis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004396","label":"Poor appetite","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002747","label":"Respiratory insufficiency due to muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011675","label":"Arrhythmia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002014","label":"Diarrhea","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000815","label":"Hypergonadotropic hypogonadism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000651","label":"Diplopia","frequency":"Excluded (0%)","criteria":null}]}}