{"orpha":496790,"name":"Ocular anomalies-axonal neuropathy-developmental delay syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Harel-Yoon syndrome"],"definition":"A rare mitochondrial disease characterized by signs and symptoms within a phenotypic and metabolic spectrum that includes global developmental delay, hypotonia, intellectual disability, optic atrophy, axonal neuropathy, hypertrophic cardiomyopathy, lactic acidosis, and increased excretion of Krebs cycle intermediates. Other variable features are spasticity, seizures, ataxia, congenital cataract, and dysmorphic facial features. Age of onset is in the neonatal period or infancy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-496790/","orphanet_url":"https://www.orpha.net/en/disease/detail/496790","names":{"fr":{"name":"Syndrome d'anomalies oculaires-neuropathie axonale-retard de développement","synonyms":["Syndrome de Harel-Yoon"],"definition":"Maladie mitochondriale rare caractérisée par des signes cliniques et des symptômes s'inscrivant dans un spectre phénotypique et métabolique comprenant un retard global du développement, une hypotonie, une déficience intellectuelle, une atrophie optique, une neuropathie axonale, une cardiomyopathie hypertrophique, une acidose lactique et une augmentation de l'excrétion des intermédiaires du cycle de Krebs. Les autres signes cliniques variables sont la spasticité, les crises convulsives, l'ataxie, la cataracte congénitale et une dysmorphie faciale. L'âge d'apparition se situe dans la période néonatale ou la petite enfance."},"de":{"name":"Optikusatrophie-periphere Neuropathie-Entwicklungsverzögerung-Syndrom","synonyms":["Harel-Yoon-Syndrom"],"definition":"Eine seltene mitochondriale Erkrankung, die durch Anzeichen und Symptome innerhalb eines phänotypischen und metabolischen Spektrums gekennzeichnet ist, das eine globale Entwicklungsverzögerung, Hypotonie, Intelligenzminderung, Optikusatrophie, axonale Neuropathie, hypertrophe Kardiomyopathie, Laktatazidose und eine erhöhte Ausscheidung von Zwischenprodukten des Krebszyklus umfasst. Weitere variable Merkmale sind Spastik, Krampfanfälle, Ataxie, kongenitaler Katarakt und Gesichtsdysmorphien. Die Krankheit beginnt in der Neugeborenenperiode oder im Säuglingsalter."},"es":{"name":"Síndrome de anomalías oculares-neuropatía axonal-retraso del desarrollo","synonyms":["Síndrome de Harel-Yoon"],"definition":"Es una enfermedad mitocondrial poco frecuente caracterizada por unos signos y síntomas comprendidos en un espectro fenotípico y metabólico que incluye retraso global del desarrollo, hipotonía, discapacidad intelectual, atrofia óptica, neuropatía axonal, miocardiopatía hipertrófica, acidosis láctica y un aumento de la excreción de intermediarios del ciclo de Krebs. Otros hallazgos variables son espasticidad, crisis epilépticas, ataxia, cataratas congénitas y rasgos faciales dismórficos. La enfermedad debuta en el período neonatal o en la lactancia."},"it":{"name":"Sindrome anomalie oculari-neuropatia assonale-ritardo dello sviluppo","definition":"Si tratta di una malattia mitocondriale rara, caratterizzata da segni clinici che rientrano in uno spettro fenotipico e metabolico che comprende il ritardo dello sviluppo globale, l'ipotonia, la disabilità intellettiva, l'atrofia ottica, la neuropatia assonale, la cardiomiopatia ipertrofica, l'acidosi lattica e un aumento dell'escrezione degli intermedi del ciclo di Krebs. I pazienti possono presentare anche spasticità, crisi epilettiche, atassia, cataratta congenita e dismorfismi facciali. La malattia esordisce nel periodo neonatale o nella prima infanzia."},"nl":{"name":"Oculaire anomalieën - axonale neuropathie - ontwikkelingsachterstand-syndroom","synonyms":["Syndroom van Harel-Yoon"],"definition":"Een zeldzame mitochondriale aandoening, gekarakteriseerd door tekenen en symptomen binnen een fenotypisch en metabool spectrum, met onder meer algehele ontwikkelingsachterstand, hypotonie, intellectuele achterstand, opticusatrofie, axonale neuropathie, hypertrofische cardiomyopathie, lactaatacidose, en verhoogde excretie van intermediairen van de Krebscyclus. Overige variabele kenmerken zijn spasticiteit, insulten, ataxie, congenitaal cataract, en dysmorfe gelaatskenmerken. De ziekte vangt aan in de neonatale periode of zuigelingentijd."},"pt":{"name":"Síndrome de atrofia óptica-neuropatia periférica-perturbação do desenvolvimento","synonyms":["Síndrome Harel-Yoon"]},"pl":{"name":"Zespół wad oczu, neuropatii aksonalnej i opóźnienia rozwoju","synonyms":["Zespół Harel i Yoona"]},"cs":{"name":"Syndrom zahrnující atrofii optiků, periferní neuropatii a vývojové opoždění","synonyms":["Harel-Yoon syndrome","Harel-Yoonův syndrom"]},"uk":{"name":"Синдром аномалій очей-аксональної нейропатії-затримки розвитку","synonyms":["Синдром Харела-Юна"],"definition":"A rare mitochondrial disease characterized by signs and symptoms within a phenotypic and metabolic spectrum that includes global developmental delay, hypotonia, intellectual disability, optic atrophy, axonal neuropathy, hypertrophic cardiomyopathy, lactic acidosis, and increased excretion of Krebs cycle intermediates. Other variable features are spasticity, seizures, ataxia, congenital cataract, and dysmorphic facial features. Age of onset is in the neonatal period or infancy."},"zh":{"name":"眼部异常-轴突神经疾病-发育迟缓综合征","synonyms":["Harel-Yoon综合征"],"definition":"一种罕见的线粒体疾病，其特征是有一些在表型和代谢相关的症状和体征，包括全球发育迟缓、肌张力低下、智力障碍、视神经萎缩、轴突性神经病、肥厚型心肌病、乳酸性酸中毒和柠檬酸循环中间产物排泄增加。其他多种特征有痉挛、癫痫、共济失调、先天性白内障、面部畸形等。发病年龄在新生儿期或婴儿期。"},"tr":{"name":"Oküler anomaliler-aksonal nöropati-gelişme geriliği sendromu","synonyms":["Harel-Yoon sendromu"]}},"xrefs":[{"source":"OMIM","code":"617183","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E88.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5D0Y","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014958","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4310677","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":217587,"name":"Mitochondrial disease with hypertrophic cardiomyopathy","classifications":[146,156,233]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":207018,"name":"Rare hereditary metabolic disease with peripheral neuropathy","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]},{"orpha":441434,"name":"Syndromic hereditary optic neuropathy","classifications":[156,189]},{"orpha":254837,"name":"Unspecified mitochondrial disorder","classifications":[150,156]}],"children":[],"genes":[{"symbol":"ATAD3A","name":"ATPase family AAA domain containing 3A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"27640307[PMID]","hgnc":"25567","ensembl":"ENSG00000197785","omim":"612316","loci":["1p36.33"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":8.0,"area":"Worldwide","status":"Validated","source":"27640307[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_27640307[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-02-06","source":"27640307[PMID]","terms":[{"hpo":"HP:0008936","label":"Axial hypotonia","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:0002151","label":"Increased circulating lactate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007210","label":"Lower limb amyotrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003477","label":"Peripheral axonal neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002064","label":"Spastic gait","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003535","label":"3-Methylglutaconic aciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000490","label":"Deeply set eye","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000823","label":"Delayed puberty","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002066","label":"Gait ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000348","label":"High forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001385","label":"Hip dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000276","label":"Long face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000303","label":"Mandibular prognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","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:0000609","label":"Optic nerve hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000768","label":"Pectus carinatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005656","label":"Positional foot deformity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007957","label":"Corneal opacity","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very rare (<4-1%)","criteria":null}]}}