{"orpha":352641,"name":"Autosomal recessive cerebellar ataxia with late-onset spasticity","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Autosomal recessive cerebellar ataxia due to GBA2 deficiency"],"definition":"A rare, genetic neurodegenerative disease characterized by childhood or adolescent-onset of cerebellar ataxia with dysarthria which slowly progresses and associates pyramidal signs, including lower limb spasticity, brisk reflexes, and Babinski and Hoffman signs. Patients typically present cerebellar ataxia with development of increasing asymmetric spasticity in upper and lower limbs, and variable axonal sensory or sensorimotor neuropathy. Additional heterogeneous features, including pes cavus, scoliolis, and abnormalities of the brain (e.g. cerebral atrophy), may also be associated.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-352641/","orphanet_url":"https://www.orpha.net/en/disease/detail/352641","names":{"fr":{"name":"Ataxie cérébelleuse autosomique récessive avec spasticité tardive","synonyms":["Ataxie cérébelleuse autosomique récessive par déficit en GBA2"],"definition":"L'ataxie cérébelleuse autosomique récessive avec spasticité tardive est une maladie génétique neurodégénérative rare caractérisée par la survenue pendant l'enfance ou à l'adolescence d'une ataxie cérébelleuse avec une dysarthrie lentement progressive, associée à des signes pyramidaux incluant une spasticité des membres inférieurs, des réflexes brusques et des signes de Babinski et d'Hoffman. Les patients présentent typiquement une ataxie cérébelleuse avec développement d'une spasticité asymétrique progressive au niveau des membres supérieurs et inférieurs, ainsi qu'une neuropathie axonale sensorielle ou sensorimotrice variable. Des signes hétérogènes peuvent aussi être associés, incluant des pieds creux, une scoliose et des anomalies cérébrales (telle qu'une atrophie cérébrale)."},"de":{"name":"Zerebelläre Ataxie, autosomal-rezessive, mit spät-einsetzender Spastik","definition":"Die autosomal-rezessive Kleinhirnataxie mit spät einsetzender Spastik ist eine seltene, genetisch bedingte neurodegenerative Erkrankung, die durch eine im Kindes- oder Jugendalter einsetzende Kleinhirnataxie mit Dysarthrie gekennzeichnet ist, die langsam fortschreitet und mit pyramidalen Zeichen, einschließlich Spastik der unteren Gliedmaßen, lebhaften Reflexen und Babinski- und Hoffman-Zeichen einhergeht. Die Patienten zeigen typischerweise eine zerebelläre Ataxie mit der Entwicklung einer zunehmenden asymmetrischen Spastik in den oberen und unteren Gliedmaßen sowie eine variable axonale sensorische oder sensomotorische Neuropathie. Zusätzliche heterogene Merkmale, einschließlich Pes cavus, Scoliolis und Anomalien des Gehirns (z. B. zerebrale Atrophie), können assoziiert sein."},"es":{"name":"Ataxia cerebelosa autosómica recesiva con espasticidad de inicio tardío","synonyms":["Ataxia cerebelosa autosómica recesiva por deficiencia de GBA2"],"definition":"Es una enfermedad neurodegenerativa, genética y poco frecuente. Está caracterizada por el inicio, en la infancia o en la adolescencia, de ataxia cerebelosa con disartria que progresa lentamente y asocia signos piramidales, incluyendo espasticidad de los miembros inferiores, reflejos exaltados y signos de Babinski y Hoffman. Los afectados típicamente presentan ataxia cerebelosa con desarrollo de espasticidad asimétrica creciente en extremidades superiores e inferiores y neuropatía axonal sensitiva o sensitivomotora variable. Otras características heterogéneas adicionales asociadas incluyen pie cavo, escoliosis y anomalías cerebrales (por ejemplo, atrofia cerebral)."},"it":{"name":"Atassia cerebellare autosomica recessiva con spasticità a esordio tardivo","synonyms":["Atassia cerebellare autosomica recessiva da deficit di GBA2"],"definition":"L'atassia cerebellare autosomica recessiva con spasticità ad esordio tardivo è una malattia neurodegenerativa rara di origine genetica, caratterizzata da atassia cerebellare con disartria a progressione lenta, associata a segni piramidali che comprendono la spasticità agli arti inferiori, la velocizzazione dei riflessi e i segni di Babinski e Hoffman; l'esordio avviene tra l'infanzia e l'adolescenza. Di solito i pazienti presentano atassia cerebellare e sviluppano una crescente spasticità asimmetrica agli arti superiori e inferiori e una neuropatia sensoriale assonale o sensitivo-motoria di grado variabile. Possono associarsi altri segni clinici eterogenei, come il piede cavo, la scoliosi e le anomalie cerebrali (atrofia del cervello)."},"nl":{"name":"Autosomaal recessieve cerebellaire ataxie met laat optredende spasticiteit","synonyms":["Autosomaal recessieve cerebellaire ataxie door GBA2-deficiëntie"],"definition":"Een zeldzame, genetische neurodegeneratieve ziekte, gekarakteriseerd door aanvang in de kindertijd of adolescentie van cerebellaire ataxie met dysartrie die traag evolueert en geassocieerd is met piramidale tekenen, waaronder spasticiteit van onderste ledematen, levendige reflexen, en tekenen van Babinski en Hoffman. Patiënten vertonen doorgaans cerebellaire ataxie met ontwikkeling van toenemende asymmetrische spasticiteit in bovenste en onderste ledematen, en variabele axonale sensorische of sensomotorische neuropathie. Bijkomende heterogene kenmerken, waaronder pes cavus, scoliose, en afwijkingen aan de hersenen (e.g. cerebrale atrofie), kunnen ook geassocieerd zijn."},"pt":{"name":"Ataxia cerebelosa com espasticidade autossómica recessiva de início tardio"},"pl":{"name":"Autosomalna recesywna ataksja móżdżkowa ze spastycznością o późnym początku","synonyms":["Autosomalna recesywna ataksja móżdżkowa z powodu niedoboru GBA2"]},"cs":{"name":"Autozomálně recesivní cerebelární ataxie se spasticitou s pozdním nástupem","synonyms":["Autozomálně recesivní cerebelární ataxie způsobená deficitem GBA2"]},"uk":{"name":"Аутосомно-рецесивна мозочкова атаксія з пізньою спастичністю","synonyms":["Аутосомно-рецесивна мозочкова атаксія внаслідок дефіциту GBA2"],"definition":"A rare, genetic neurodegenerative disease characterized by childhood or adolescent-onset of cerebellar ataxia with dysarthria which slowly progresses and associates pyramidal signs, including lower limb spasticity, brisk reflexes, and Babinski and Hoffman signs. Patients typically present cerebellar ataxia with development of increasing asymmetric spasticity in upper and lower limbs, and variable axonal sensory or sensorimotor neuropathy. Additional heterogeneous features, including pes cavus, scoliolis, and abnormalities of the brain (e.g. cerebral atrophy), may also be associated."},"zh":{"name":"常染色体隐性遗传性小脑共济失调伴迟发性痉挛","synonyms":["GBA2缺乏所致常染色体隐性遗传性小脑共济失调"],"definition":"本病是一种罕见的遗传性神经退行性疾病，以儿童或青少年期起病的小脑性共济失调为特征，伴有缓慢进展的构音障碍，并与锥体束征相关，包括下肢痉挛、反射亢进、巴宾斯基征和霍夫曼征。患者的典型表现为小脑性共济失调，进行性上下肢不对称痉挛，以及可变的轴突感觉或感觉运动性神经病。其他的异质性特征如腔静脉畸形、脊柱侧凸和脑的异常(如脑萎缩)，也可能与此相关。"},"tr":{"name":"Geç başlangıçlı spastisite ile seyreden otozomal resesif serebellar ataksi","synonyms":["GBA2 eksikliğine bağlı otozomal çekinik serebellar ataksi"]}},"xrefs":[{"source":"ICD-10","code":"G11.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8A03.1Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0018129","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4706412","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":98096,"name":"Autosomal recessive metabolic cerebellar ataxia","classifications":[156,181]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":79225,"name":"Sphingolipidosis","classifications":[150,156,233]}],"children":[],"genes":[{"symbol":"GBA2","name":"glucosylceramidase beta 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"23332917[PMID]","hgnc":"18986","ensembl":"ENSG00000070610","omim":"609471","loci":["9p13.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Adolescent","Childhood"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":10.0,"area":"Worldwide","status":"Validated","source":"23332917[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":"2018-11-05","source":"23332917[PMID]_24252062[PMID]","terms":[{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002073","label":"Progressive cerebellar ataxia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000570","label":"Abnormal saccadic eye movements","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001348","label":"Brisk reflexes","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002066","label":"Gait ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010831","label":"Impaired proprioception","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002061","label":"Lower limb spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003477","label":"Peripheral axonal neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007141","label":"Sensorimotor neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002464","label":"Spastic dysarthria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003693","label":"Distal amyotrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002346","label":"Head tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002166","label":"Impaired vibration sensation in the lower limbs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000020","label":"Urinary incontinence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001256","label":"Intellectual disability, mild","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002078","label":"Truncal ataxia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0004905","label":"Low levels of vitamin A","frequency":"Excluded (0%)","criteria":null},{"hpo":"HP:0100513","label":"Low levels of vitamin E","frequency":"Excluded (0%)","criteria":null}]}}