{"orpha":309256,"name":"Metachromatic leukodystrophy, late infantile form","type":"Clinical subtype","group":"Subtype of disorder","status":"active","flags":[],"synonyms":["Arylsulfatase A deficiency, late infantile form","MLD, late infantile form"],"definition":"A subtype of Metachromatic leukodystrophy characterized by rapidly progressive psychomotor regression with an onset before 30 months of age after a period of apparently normal development. Manifestations developing during the course of the disease are impaired feeding and swallowing due to pseudobulbar palsies, seizures, painful spasms, muscle weakness, ataxia, paralysis, dementia, and loss of speech, vision, and hearing, quickly resulting in complete loss of motor and cognitive skills, and decerebration. Death occurs within the first decade of life.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-309256/","orphanet_url":"https://www.orpha.net/en/disease/detail/309256","names":{"fr":{"name":"Leucodystrophie métachromatique infantile tardive","synonyms":["Déficit en arylsulfatase A, forme infantile tardive","MLD, forme infantile tardive"],"definition":"Sous-type de leucodystrophie métachromatique caractérisé par une régression psychomotrice rapidement progressive se manifestant avant l'âge de 30 mois après une période de développement normale. Les manifestations observées au cours de la maladie sont des troubles de l'alimentation et de la déglutition dus à des paralysies pseudobulbaires, des crises convulsives, des douleurs spasmodiques, une faiblesse musculaire, une ataxie, une paralysie, une démence et une aphasie, des troubles de la vue et de l'audition, aboutissant rapidement à une perte complète des capacités motrices et cognitives, et à une décérébration. Le décès survient au cours de la première décennie de vie."},"de":{"name":"Leukodystrophie, metachromatische, spät-infantile Form","synonyms":["Arylsulfatase A-Mangel, spät-infantile Form","MLD, spät-infantile Form"],"definition":"Ein Subtyp der metachromatischen Leukodystrophie, der durch eine schnell fortschreitende psychomotorische Regression gekennzeichnet ist und vor dem 30. Lebensmonat nach einer Phase scheinbar normaler Entwicklung einsetzt. Im Verlauf der Krankheit entwickeln sich Manifestationen wie Fütterungs- und Schluckstörungen aufgrund von Pseudobulbärparesen, Krampfanfällen, schmerzhaften Spasmen, Muskelschwäche, Ataxie, Lähmungen, Demenz und Sprach-, Seh- und Hörverlust, die schnell zu einem vollständigen Verlust der motorischen und kognitiven Fähigkeiten und zur Dezerebration führen. Der Tod tritt innerhalb des ersten Lebensjahrzehnts ein."},"es":{"name":"Leucodistrofia metacromática, forma infantil tardía","synonyms":["Deficiencia de arilsulfatasa A, forma infantil tardía","MLD, forma infantil tardía"],"definition":"Es un subtipo de leucodistrofia metacromática caracterizado por una regresión psicomotora rápidamente progresiva que debuta antes de los 30 meses de edad, tras un período de desarrollo aparentemente normal. Las manifestaciones que se desarrollan durante el curso de la enfermedad son dificultad en la alimentación y de la deglución debido a la parálisis pseudobulbar, crisis epilépticas, espasmos dolorosos, debilidad muscular, ataxia, parálisis, demencia y pérdida auditiva, de la visión y del habla, que progresan rápidamente a una pérdida completa de las habilidades motoras y cognitivas y a descerebración. La muerte se produce durante la primera década de la vida."},"it":{"name":"Leucodistrofia metacromatica, forma infantile tardiva","synonyms":["Deficit di arilsulfatasi A, forma infantile tardiva","MLD, forma infantile tardiva"],"definition":"Si tratta di un sottotipo della leucodistrofia metacromatica, caratterizzato da regressione psicomotoria a progressione rapida, che esordisce prima dei 30 mesi di vita, dopo un periodo di sviluppo apparentemente normale. I segni clinici comprendono le difficoltà di alimentazione e di deglutizione secondarie alla paralisi pseudobulbare, le crisi epilettiche, gli spasmi dolorosi, la debolezza muscolare, l'atassia, la paralisi, la demenza, la perdita del linguaggio, della vista e dell'udito, che esitano rapidamente nella perdita completa delle competenze motorie e cognitive e nella decerebrazione. La morte avviene nella prima decade."},"nl":{"name":"Metachromatische leukodystrofie, late infantiele vorm","synonyms":["Arylsulfatase A-deficiëntie, late infantiele vorm","MLD, late infantiele vorm"],"definition":"Een subtype van metachromatische leukodystrofie, gekarakteriseerd door snel progressieve psychomotorische regressie met aanvang voor de leeftijd van 30 maanden na een periode van schijnbaar normale ontwikkeling. Manifestaties die zich ontwikkelen tijdens het verloop van de ziekte zijn voedings- en slikproblemen als gevolg van pseudobulbaire paralyse, insulten, pijnlijke spasmen, spierzwakte, ataxie, verlamming, dementie, verlies van spraak, zicht en gehoor, wat al snel leidt tot volledig verlies van motorische en cognitieve vaardigheden, en decerebratie. Overlijden vindt plaats tijdens het eerste levensdecennium."},"pt":{"name":"Leucodistrofia metacromática, forma da infância tardia"},"pl":{"name":"Leukodystrofia metachromatyczna, postać niemowlęca późna","synonyms":["MLD, postać niemowlęca późna","Niedobór arylsulfatazy A, postać niemowlęca późna"]},"cs":{"name":"Metachromatická leukodystrofie, forma pozdně infantilní","synonyms":["Deficit arylsulfatázy A, forma pozdně infantilní","MLD, forma pozdně infantilní"]},"uk":{"name":"Метахроматична лейкодистрофія, пізня інфантильна форма","synonyms":["Дефіцит арилсульфатази А, пізня інфантильна форма","Пізня дитяча форма, пізня інфантильна форма"],"definition":"A subtype of Metachromatic leukodystrophy characterized by rapidly progressive psychomotor regression with an onset before 30 months of age after a period of apparently normal development. Manifestations developing during the course of the disease are impaired feeding and swallowing due to pseudobulbar palsies, seizures, painful spasms, muscle weakness, ataxia, paralysis, dementia, and loss of speech, vision, and hearing, quickly resulting in complete loss of motor and cognitive skills, and decerebration. Death occurs within the first decade of life."},"zh":{"name":"婴儿晚期型异染性脑白质营养不良","synonyms":["婴儿晚期型芳香硫酸酯酶A缺乏"],"definition":"异染性脑白质营养不良的一种亚型，以快速进行性的精神运动退化为特征，发病年龄在30个月前，发病前发育正常。疾病表现为假性延髓麻痹、癫痫、疼痛性痉挛、肌无力、共济失调、瘫痪、痴呆、语言、视力和听力丧失导致进食和吞咽障碍，很快导致完全丧失运动和认知能力，以及去大脑状态。死亡发生在生命的前十年。"},"tr":{"name":"Metakromatik lökodistrofi, geç infantil formu","synonyms":["MLD, geç infantil formu","Arilsülfataz A eksikliği, geç infantil formu"]}},"xrefs":[{"source":"OMIM","code":"250100","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E75.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C56.02","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"422777002"},{"source":"MONDO","code":"0017729","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0751278","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":512,"name":"Metachromatic leukodystrophy","classifications":[150,156,181,189,233]}],"children":[],"genes":[{"symbol":"ARSA","name":"arylsulfatase A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301309[PMID]","hgnc":"713","ensembl":"ENSG00000100299","omim":"607574","loci":["22q13.33"]},{"symbol":"PSAP","name":"prosaposin","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24478108[PMID]","hgnc":"9498","ensembl":"ENSG00000197746","omim":"176801","loci":["10q22.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Prevalence at birth","qualification":"Class only","class":"1-9 / 1 000 000","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"ORPHANET_24001781[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2018-03-19","source":"20038527[PMID]_21707604[PMID]_14206875[PMID]","terms":[{"hpo":"HP:0002312","label":"Clumsiness","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000762","label":"Decreased nerve conduction velocity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003444","label":"EMG: chronic denervation signs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002359","label":"Frequent falls","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0002066","label":"Gait ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002922","label":"Increased CSF protein concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002415","label":"Leukodystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007240","label":"Progressive gait ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007133","label":"Progressive peripheral neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030081","label":"Punctate periventricular T2 hyperintense foci","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030051","label":"Tip-toe gait","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000020","label":"Urinary incontinence","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003270","label":"Abdominal distention","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012433","label":"Abnormal social behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001939","label":"Abnormality of metabolism/homeostasis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000649","label":"Abnormality of visual evoked potentials","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008619","label":"Bilateral sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001082","label":"Cholecystitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000746","label":"Delusion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000712","label":"Emotional lability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000738","label":"Hallucinations","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002371","label":"Loss of speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007663","label":"Reduced visual acuity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025013","label":"Decerebrate rigidity","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0031358","label":"Vegetative state","frequency":"Very rare (<4-1%)","criteria":null}]}}