{"orpha":447997,"name":"Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["ASCT1 deficiency","Spastic quadriplegia-thin corpus callosum-progressive postnatal microcephaly syndrome"],"definition":"A rare neurometabolic disorder due to serine deficiency characterized by neonatal to infantile onset of global developmental delay, postnatal microcephaly and intellectual disability, which may be associated with slowly progressive spastic tetraplegia mainly affecting the lower extremities, seizures, and brain MRI findings including thin corpus callosum, delayed myelination and cerebral atrophy. Additional symptoms include brisk deep tendon reflexes, extensor plantar responses, behavioral abnormalities (such as irritability, hyperactivity, sleep disorder), abnormal hand movements and stereotypy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-447997/","orphanet_url":"https://www.orpha.net/en/disease/detail/447997","names":{"fr":{"name":"Syndrome tétraplégie spastique-corps calleux fin-microcéphalie postnatale progressive","synonyms":["Déficit en ASCT1","Syndrome de quadriplégie spastique-corps calleux fin-microcéphalie postnatale progressive"],"definition":"Maladie neurométabolique par déficit en sérine caractérisée par l'apparition néonatale à infantile d'un retard global de développement, d'une microcéphalie postnatale et d'une déficience intellectuelle, qui peut être associée à une tétraplégie spastique lentement progressive affectant principalement les membres inférieurs, à des crises convulsives et à des anomalies identifiées à l'IRM cérébrale, à savoir, un corps calleux mince, un retard de myélinisation et une atrophie cérébrale. Les autres signes cliniques sont des réflexes tendineux profonds vifs, des réponses plantaires en extention, des troubles du comportement (tels que l'irritabilité, l'hyperactivité, les troubles du sommeil), des mouvements anormaux des mains et la stéréotypie."},"de":{"name":"Spastische Tetraplegie-dünnes Corpus callosum-progressive postnatale Mikrozephalie-Syndrom","synonyms":["ASCT1-Mangel"],"definition":"Eine durch Serinmangel bedingte seltene neurometabolische Störung, die durch eine neonatale bis infantile globale Entwicklungsverzögerung, postnatale Mikrozephalie und Intelligenzminderung gekennzeichnet ist, die mit einer langsam fortschreitenden spastischen Tetraplegie, die hauptsächlich die unteren Extremitäten betrifft, Krampfanfällen und MRT-Befunden des Gehirns einschließlich dünnem Corpus callosum, verzögerter Myelinisierung und zerebraler Atrophie einhergehen kann. Zu den weiteren Symptomen gehören lebhafte tiefe Sehnenreflexe, extensorische Plantarreflexe, Verhaltensauffälligkeiten (wie Reizbarkeit, Hyperaktivität, Schlafstörungen), abnorme Handbewegungen und Stereotypie."},"es":{"name":"Síndrome de tetraplejía espástica-cuerpo calloso delgado-microcefalia progresiva postnatal","synonyms":["Deficiencia de ASCT1","Síndrome de cuadriplejía espástica-cuerpo calloso delgado-microcefalia progresiva postnatal"],"definition":"Es un trastorno neurometabólico poco frecuente debido a una deficiencia de serina que se caracteriza por un retraso global del desarrollo, microcefalia posnatal y discapacidad intelectual de inicio neonatal a infantil, que puede estar asociado a tetraplejía espástica lentamente progresiva que afecta principalmente a las extremidades inferiores, crisis y alteraciones en la RM cerebral, incluyendo adelgazamiento del cuerpo calloso, retraso en la mielinización y atrofia cerebral. Otros síntomas adicionales incluyen reflejos tendinosos profundos vivos, respuestas plantares extensoras, trastornos de la conducta (como irritabilidad, hiperactividad, alteraciones del sueño), movimientos anormales de las manos y estereotipias."},"it":{"name":"Sindrome tetraplegia spastica-assottigliamento del corpo calloso-microcefalia postnatale progressiva","synonyms":["Deficit di ASCT1","Sindrome quadriplegia spastica-corpo calloso sottile-microcefalia postnatale progressiva"],"definition":"Si tratta di una malattia neurometabolica rara, causata da un deficit di serina, caratterizzata da ritardo dello sviluppo globale ad esordio neonatale o infantile, microcefalia postnatale e disabilità intellettiva, che possono associarsi a tetraplegia spastica a progressione lenta, che colpisce per lo più gli arti inferiori, e crisi epilettiche; la RMN evidenzia l'assottigliamento del corpo calloso, il ritardo della mielinizzazione e l'atrofia cerebrale. I pazienti possono anche presentare vivaci riflessi tendinei profondi, risposte plantari in estensione, anomalie del comportamento (irritabilità, iperattività, disturbi del sonno), anomali movimenti della mano e stereotipie."},"nl":{"name":"Spastische tetraplegie - dun corpus callosum - progressieve postnatale microcefalie-syndroom","synonyms":["ASCT1-deficiëntie","Spastische quadriplegie - dun corpus callosum - progressieve postnatale microcefalie-syndroom"],"definition":"Een zeldzame neurometabole aandoening door serinedeficiëntie, gekarakteriseerd door neonatale tot infantiele aanvang van algehele ontwikkelingsachterstand, postnatale microcefalie en intellectuele achterstand, mogelijk geassocieerd met traag progressieve spastische tetraplegie van vooral onderste ledematen, insulten, en MRI van hersenen die onder meer dun corpus callosum, vertraagde myelinisatie en cerebrale atrofie toont. Bijkomende symptomen zijn onder meer hoge diepe peesreflexen, voetzoolreflexen in extensie, gedragsafwijkingen (zoals prikkelbaarheid, hyperactiviteit, slaapstoornis), abnormale handbewegingen en stereotypie."},"pt":{"name":"Síndrome de tetraplegia espástica-corpo caloso estreito-microcefalia pós-natal progressiva"},"pl":{"name":"Zespół tetraplegii spastycznej, cienkego ciała modzelowatego i postępującej mikrocefalii postnatalnej","synonyms":["Niedobór ASCT1","Zespół kwadriplegii spastycznej, cienkego ciała modzelowatego i postępującej mikrocefalii postnatalnej"]},"cs":{"name":"Syndrom zahrnující spastickou tetraplegii, tenké corpus callosum a progresivní postnatální mikrocefalii","synonyms":["ASCT1 deficit","Syndrom zahrnující spastickou kvadruplegii, tenké corpus callosum a progresivní postnatální mikrocefalii"]},"uk":{"name":"Синдром спастичноїа тетраплегії-тонкого мозолистого тіла-прогресуючої постнатальної мікроцефалії","synonyms":["Дефіцит ASCT1","Синдром спастичної квадриплегії - тонкого мозолистого тіла - прогресуючої постнатальної мікроцефалії"],"definition":"A rare neurometabolic disorder due to serine deficiency characterized by neonatal to infantile onset of global developmental delay, postnatal microcephaly and intellectual disability, which may be associated with slowly progressive spastic tetraplegia mainly affecting the lower extremities, seizures, and brain MRI findings including thin corpus callosum, delayed myelination and cerebral atrophy. Additional symptoms include brisk deep tendon reflexes, extensor plantar responses, behavioral abnormalities (such as irritability, hyperactivity, sleep disorder), abnormal hand movements and stereotypy."},"zh":{"name":"痉挛性四肢瘫痪-胼胝体发育不良-生后进行性小头畸形","synonyms":["ASCT1缺乏"],"definition":"丝氨酸缺乏引起的罕见神经代谢异常，其特征为新生儿至婴儿发作，发育迟缓，出生后小头畸形和智力残疾，可能与缓慢进行性痉挛性四肢瘫痪有关，主要影响下肢，此外还有癫痫发作，头颅MRI发现包括胼胝体薄，髓鞘形成延迟和脑萎缩。其他症状包括兴奋性深部肌腱反射，巴氏征阳性，行为异常（例如烦躁，多动，睡眠障碍），异常手部动作和刻板行为。"},"tr":{"name":"Spastik tetrapleji-ince korpus kallozum-ilerleyici doğum sonrası mikrosefali sendromu","synonyms":["Spastik kuadripleji-ince korpus kallozum-İlerleyici doğum sonrası mikrosefali sendromu","ASCT1 eksikliği"]}},"xrefs":[{"source":"OMIM","code":"616657","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E72.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-10","code":"Q02","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C50.6","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0014725","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4225254","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"13425","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68416,"name":"Rare infectious disease"},"parents":[{"orpha":35705,"name":"Neurometabolic disorder due to serine deficiency","classifications":[150,156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"SLC1A4","name":"solute carrier family 1 member 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"25930971[PMID]_26041762[PMID]_26138499[PMID]","hgnc":"10942","ensembl":"ENSG00000115902","omim":"600229","loci":["2p14"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":15.0,"area":"Worldwide","status":"Validated","source":"25930971[PMID]_26041762[PMID]_26138499[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_25930971[PMID]_26041762[PMID]_26138499[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-12-09","source":"31763347[PMID]_29989513[PMID]_27161889[PMID]_26041762[PMID]","terms":[{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012444","label":"Brain atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002061","label":"Lower limb spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011451","label":"Primary microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005484","label":"Secondary microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006808","label":"Cerebral hypomyelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002169","label":"Clonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011471","label":"Gastrostomy tube feeding in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012167","label":"Hair-pulling","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000752","label":"Hyperactivity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002521","label":"Hypsarrhythmia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000737","label":"Irritability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002828","label":"Multiple joint contractures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003739","label":"Myoclonic spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000411","label":"Protruding ear","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002205","label":"Recurrent respiratory infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000664","label":"Synophrys","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000020","label":"Urinary incontinence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Occasional (29-5%)","criteria":null}]}}