{"orpha":496756,"name":"Early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare genetic neurodegenerative disease characterized by neonatal to infantile onset of hypotonia, developmental delay, regression of motor skills with distal amyotrophy, ataxia, and spasticity, absent speech or dysarthria, and moderate to severe cognitive impairment. Optic atrophy may also be associated. Brain imaging shows cerebellar atrophy and thin corpus callosum, as well as brain iron accumulation in the pallidum and substantia nigra beginning during the second decade of life.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-496756/","orphanet_url":"https://www.orpha.net/en/disease/detail/496756","names":{"fr":{"name":"Syndrome d'encéphalopathie progressive à début précoce-ataxie spastique-amyotrophie spinale distale","definition":"Maladie neurodégénérative génétique rare, caractérisée par l'apparition néonatale à infantile d'une hypotonie, d'un retard de développement, d'une régression des capacités motrices avec une amyotrophie distale, d'une ataxie et d'une spasticité, d'une absence du langage ou d'une dysarthrie, et des troubles cognitifs modérés à sévères. Une atrophie optique peut également être associée. L'IRM révèle une atrophie cérébelleuse et une dysgénésie du corps calleux, ainsi qu'une accumulation de fer dans le cerveau, notamment dans le pallidum et la substantia nigra à partir de la deuxième décennie de vie."},"de":{"name":"Früh-beginnende progressive Enzephalopathie-spastische Ataxie-distale spinale Muskelatrophie-Syndrom","definition":"Eine seltene genetisch bedingte neurodegenerative Erkrankung, die durch Hypotonie, Entwicklungsverzögerung, Rückbildung der motorischen Fähigkeiten mit distaler Amyotrophie, Ataxie und Spastik, fehlende Sprache oder Dysarthrie und mäßige bis schwere kognitive Beeinträchtigung gekennzeichnet ist. Auch eine Optikusatrophie kann damit verbunden sein. Die Bildgebung des Gehirns zeigt eine Atrophie des Kleinhirns und ein dünnes Corpus callosum sowie eine Eisenanreicherung im Pallidum und in der Substantia nigra, die im zweiten Lebensjahrzehnt beginnt."},"es":{"name":"Síndrome de encefalopatía progresiva-ataxia espástica-atrofia muscular espinal distal de inicio precoz","definition":"Es una enfermedad neurodegenerativa de origen genético poco frecuente caracterizada por hipotonía de inicio neonatal o en la lactancia, retraso psicomotor, regresión de las habilidades motoras acompañado de amiotrofia distal, ataxia y espasticidad, ausencia del habla o disartria y deterioro cognitivo de moderado a grave. El síndrome también puede asociar atrofia óptica. La neuroimagen muestra atrofia cerebelosa y adelgazamiento del calloso delgado, así como acúmulos cerebrales de hierro en el globo pálido y la sustancia negra, que aparecen durante la segunda década de la vida."},"it":{"name":"Sindrome encefalopatia progressiva ad esordio precoce-atassia spastica-atrofia muscolare spinale distale","definition":"Si tratta di una malattia neurodegenerativa genetica rara, che esordisce nel periodo neonatale o nella prima infanzia con ipotonia, ritardo dello sviluppo, regressione delle competenze motorie con amiotrofia distale, atassia, spasticità, assenza del linguaggio o disartria, e deficit cognitivo moderato-grave. Può associarsi ad atrofia ottica. Le neuroimmagini mostrano atrofia cerebellare, assottigliamento del corpo calloso e depositi di ferro nel globo pallido e nella substantia nigra a partire dalla seconda decade di vita."},"nl":{"name":"Progressieve encefalopathie met vroege aanvang - spastische ataxie - distale spinale musculaire atrofie-syndroom","definition":"Een zeldzame, genetische neurodegeneratieve aandoening, gekarakteriseerd door neonatale tot infantiele aanvang van hypotonie, ontwikkelingsachterstand, regressie van motorische vaardigheden met distale amyotrofie, ataxie en spasticiteit, afwezigheid van spraak of dysartrie, en matige tot ernstige cognitieve functiestoornis. Opticusatrofie kan ook geassocieerd zijn. Beeldvorming van hersenen toont cerebellaire atrofie en dun corpus callosum, alsook accumulatie van ijzer in pallidum en substantia nigra vanaf het tweede levensdecennium."},"pt":{"name":"Síndrome de encefalopatia progressiva de início precoce-ataxia espástica-atrofia muscular espinhal distal"},"pl":{"name":"Zespół wczesnej i postępującej encefalopatii, ataksji spastycznej, dystalnej atrofii mięśniowo-rdzeniowej"},"cs":{"name":"Syndrom zahrnující progresivní encefalopatii s časným nástupem, spastickou ataxii a spinální muskulární atrofii"},"uk":{"name":"Синдром ранньої прогресуючої енцефалопатії-спастичної атаксії-дистальної спінальної мязової атрофії","definition":"A rare genetic neurodegenerative disease characterized by neonatal to infantile onset of hypotonia, developmental delay, regression of motor skills with distal amyotrophy, ataxia, and spasticity, absent speech or dysarthria, and moderate to severe cognitive impairment. Optic atrophy may also be associated. Brain imaging shows cerebellar atrophy and thin corpus callosum, as well as brain iron accumulation in the pallidum and substantia nigra beginning during the second decade of life."},"zh":{"name":"早发性进行性脑病-痉挛性共济失调-远端脊髓性肌萎缩症","definition":"一种罕见的遗传性神经退行性疾病，其特征是新生儿至婴儿期开始出现肌张力低下，发育迟缓，运动能力倒退，伴有远端肌萎缩、共济失调和痉挛，失语或构音障碍，中度至重度认知障碍。还可能伴有视神经萎缩。脑影像学检查显示小脑萎缩和胼胝体变薄，以及从出生后20岁开始，脑中铁在苍白球和黑质中积聚。"},"tr":{"name":"Erken başlangıçlı ilerleyici ensefalopati-spastik ataksi-distal spinal musküler atrofi sendromu"}},"xrefs":[{"source":"OMIM","code":"617207","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G31.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0044651","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5567451","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":98098,"name":"Autosomal recessive degenerative and progressive cerebellar ataxia","classifications":[156,181]},{"orpha":140468,"name":"Autosomal recessive distal hereditary motor neuropathy","classifications":[156,181]},{"orpha":385,"name":"Neurodegeneration with brain iron accumulation","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"TBCE","name":"tubulin folding cofactor E","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"27666369[PMID]","hgnc":"11582","ensembl":"ENSG00000284770","omim":"604934","loci":["1q42.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":6.0,"area":"Worldwide","status":"Validated","source":"27666369[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_27666369[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2018-11-26","source":"27666369[PMID]","terms":[{"hpo":"HP:0003693","label":"Distal amyotrophy","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0002448","label":"Progressive encephalopathy","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0002497","label":"Spastic ataxia","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0007269","label":"Spinal muscular atrophy","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001272","label":"Cerebellar atrophy","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:0001260","label":"Dysarthria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003444","label":"EMG: chronic denervation signs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009027","label":"Foot dorsiflexor weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003477","label":"Peripheral axonal neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002425","label":"Anarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012678","label":"Iron accumulation in substantia nigra","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007199","label":"Progressive spastic paraparesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001285","label":"Spastic tetraparesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Excluded (0%)","criteria":null},{"hpo":"HP:0000829","label":"Hypoparathyroidism","frequency":"Excluded (0%)","criteria":null}]}}