{"orpha":320391,"name":"Autosomal recessive spastic paraplegia type 46","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["SPG46"],"definition":"Autosomal recessive spastic paraplegia type 46 (SPG46) is a rare, complex type of hereditary spastic paraplegia characterized by an onset, in infancy or childhood, of the typical signs of spastic paraplegia (i.e. spastic gait and weakness of the lower limbs) associated with a variety of additional manifestations including upper limb spasticity and weakness, pseudobulbar dysarthria, bladder dysfunction, cerebellar ataxia, cataracts, and cognitive impairment that can progress to dementia. Brain imaging may show thinning of the corpus callosum and mild atrophy of the cerebrum and cerebellum. SPG46 is due to mutations in the <i>GBA2</i> gene (9p13.2) encoding non-lysosomal glucosylceramidase.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-320391/","orphanet_url":"https://www.orpha.net/en/disease/detail/320391","names":{"fr":{"name":"Paraplégie spastique autosomique récessive type 46","synonyms":["SPG46"],"definition":"Type rare et complexe de paraplégie spastique héréditaire caractérisé par l'apparition, dans la petite enfance ou l'enfance, des signes typiques de paraplégie spastique (à type de démarche spastique et de faiblesse des membres inférieurs) associés à différents autres signes, notamment une spasticité et une faiblesse des membres supérieurs, une dysarthrie pseudobulbaire, un dysfonctionnement de la vessie, une ataxie cérébelleuse, des cataractes et des troubles cognitifs qui peuvent évoluer vers la démence. L'imagerie cérébrale peut mettre en évidence un corps calleux fin et une légère atrophie cérébrale et cérébelleuse. La SPG46 (pour spastic paraplegia type&nbsp;46 ) est due à des mutations du gène <i>GBA2</i> (9p13.2) codant pour une glucosylcéramidase non lysosomale."},"de":{"name":"Spastische Paraplegie, autosomal-rezessive, Typ 46","synonyms":["SPG46"],"definition":"Die autosomal-rezessive spastische Paraplegie Typ 46 (SPG46) ist eine seltene, komplexe Form der hereditären spastischen Paraplegie, welche sich durch einen Beginn von typischen Symptomen der spastischen Paraplegie (d. h. spastischer Gang und Schwäche der oberen Extremitäten) im Kleinkind- oder Kindesalter sowie einer Vielzahl von zusätzlichen Manifestationen wie Spastik und Schwäche der oberen Extremitäten, pseudobulbäre Dysarthrie, Blasendysfunktion, zerebelläre Ataxie, Katarakt und kognitive Einschränkung, die zur Demenz führen kann, auszeichnet. Bildgebungen des Gehirns zeigen Ausdünnungen des Corpus Callosum und eine leichte Atrophie des Cerebellums und des Cerebrums."},"es":{"name":"Paraparesia espástica autosómica recesiva tipo 46","synonyms":["SPG46","Paraplejía espástica autosómica recesiva tipo 46"],"definition":"Es un tipo poco frecuente y complejo de paraplejía espástica hereditaria caracterizada por el inicio, en la lactancia, de los signos típicos de paraplejía espástica (es decir, marcha espástica y debilidad de las extremidades inferiores) asociada a una variedad de manifestaciones adicionales que incluyen espasticidad y debilidad de las extremidades superiores, disartria pseudo-bulbar, disfunción de la vejiga, ataxia cerebelosa, cataratas y deterioro cognitivo que puede progresar a demencia. La neuroimagen cerebral puede mostrar adelgazamiento del cuerpo calloso y leve atrofia del cerebro y del cerebelo. La enfermedad está causada por mutaciones en el gen <i>GBA2</i> (9p13.2), que codifica para la glucosilceramidasa no lisosomal."},"it":{"name":"Paraplegia spastica autosomica recessiva, tipo 46","synonyms":["SPG46"],"definition":"La paraplegia spastica autosomica recessiva tipo 46 (SPG46) è una forma rara e complessa di paraplegia spastica ereditaria, caratterizzata dall'esordio, in epoca neonatale o infantile, dei segni caratteristici della paraplegia spastica (andatura spastica e debolezza degli arti inferiori), associati a spasticità e debolezza degli arti superiori, disartria pseudo-bulbare, disfunzione della vescica, atassia cerebellare, cataratta e deterioramento cognitivo che può esitare nella demenza. Le immagini diagnostiche del cervello possono evidenziare un assottigliamento del corpo calloso e una lieve atrofia del cervello e del cervelletto. La SPG46 è causata dalle mutazioni nel gene GBA2 che codifica la glucosilceramidasi non lisosomiale."},"nl":{"name":"Autosomaal recessieve spastische paraplegie type 46","synonyms":["SPG46"],"definition":"Autosomaal recessieve spastische paraplegie type 46 (SPG46) is een zeldzaam, complex type van erfelijke spastische paraplegie dat gekarakteriseerd wordt door aanvang in de zuigelingen- of kindertijd van de typische tekenen van spastische paraplegie (i.e. spastische gang en zwakte van de onderste ledematen), geassocieerd met een verscheidenheid aan bijkomende manifestaties waaronder spasticiteit en zwakte van de bovenste ledematen, pseudobulbaire dysartrie, blaasdisfunctie, cerebellaire ataxie, cataract, en cognitieve beperkingen die tot dementie kunnen evolueren. Beeldvorming van de hersenen toont verdunning van het corpus callosum en milde atrofie van het cerebrum en het cerebellum. SPG46 is het gevolg van mutaties in het gen <i>GBA2</i> (9p13.2), dat codeert voor niet-lysosomaal glucosylceramidase."},"pt":{"name":"Paraplegia espástica autossómica recessiva tipo 46"},"pl":{"name":"Autosomalna recesywna paraplegia spastyczna typu 46","synonyms":["SPG46"]},"cs":{"name":"Autozomálně recesivní spastická paraplegie, typ 46","synonyms":["SPG46"]},"uk":{"name":"Аутосомно-рецесивна спастична параплегія, тип 46","synonyms":["SPG46"],"definition":"Autosomal recessive spastic paraplegia type 46 (SPG46) is a rare, complex type of hereditary spastic paraplegia characterized by an onset, in infancy or childhood, of the typical signs of spastic paraplegia (i.e. spastic gait and weakness of the lower limbs) associated with a variety of additional manifestations including upper limb spasticity and weakness, pseudobulbar dysarthria, bladder dysfunction, cerebellar ataxia, cataracts, and cognitive impairment that can progress to dementia. Brain imaging may show thinning of the corpus callosum and mild atrophy of the cerebrum and cerebellum. SPG46 is due to mutations in the <i>GBA2</i> gene (9p13.2) encoding non-lysosomal glucosylceramidase."},"zh":{"name":"常染色体隐性遗传痉挛性截瘫46型","synonyms":["SPG46"],"definition":"常染色体隐性痉挛性截瘫46型(SPG46)是一种罕见的复杂类型的遗传性痉挛性截瘫，其特征是在婴儿期或儿童期出现痉挛性截瘫的典型症状(即痉挛性步态和下肢无力)，并伴有多种其他表现，包括上肢痉挛和无力、假性球麻痹、膀胱功能障碍、小脑性共济失调、白内障和可发展为痴呆的认知障碍。脑成像可能显示胼胝体变薄，大脑和小脑轻度萎缩。SPG46是由于编码非溶酶体葡糖神经酰胺酶的基因GBA2 (9p13.2)突变引起的。"},"tr":{"name":"Otozomal resesif spastik parapleji tip 46","synonyms":["SPG46"]}},"xrefs":[{"source":"OMIM","code":"614409","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G11.4","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8B44.01","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0013737","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2828721","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"17476","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":100981,"name":"Autosomal recessive complex spastic paraplegia","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"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":"23332916[PMID]","hgnc":"18986","ensembl":"ENSG00000070610","omim":"609471","loci":["9p13.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Childhood","Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":5.0,"area":"Worldwide","status":"Validated","source":"20593214[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_20593214[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2018-04-05","source":"23332916[PMID]_23332917[PMID]_24252062[PMID]","terms":[{"hpo":"HP:0001251","label":"Ataxia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002061","label":"Lower limb spasticity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002500","label":"Abnormal cerebral white matter morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007371","label":"Corpus callosum atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012864","label":"Abnormal sperm morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100261","label":"Abnormal tendon morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002136","label":"Broad-based gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008734","label":"Decreased testicular size","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000726","label":"Dementia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002346","label":"Head tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006938","label":"Impaired vibration sensation at ankles","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000789","label":"Infertility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008003","label":"Jerky ocular pursuit movements","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003477","label":"Peripheral axonal neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012207","label":"Reduced sperm motility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002464","label":"Spastic dysarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012865","label":"Sperm head anomaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002078","label":"Truncal ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006986","label":"Upper limb spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000020","label":"Urinary incontinence","frequency":"Occasional (29-5%)","criteria":null}]}}