{"orpha":512,"name":"Metachromatic leukodystrophy","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Arylsulfatase A deficiency","MLD"],"definition":"A rare lysosomal disease characterized by accumulation of sulfatides in the central and peripheral nervous system due to deficiency of the enzyme arylsulfatase A, leading to demyelination. Three clinical subtypes can be distinguished based on the age of onset: late infantile, juvenile, and adult. Lead symptoms are deterioration in motor or cognitive function or behavioral problems, depending on the subtype, all eventually culminating in a decerebrated state and death after a highly variable disease course and duration. Mode of inheritance is autosomal recessive.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-512/","orphanet_url":"https://www.orpha.net/en/disease/detail/512","names":{"fr":{"name":"Leucodystrophie métachromatique","synonyms":["Déficit en arylsulfatase A","MLD"],"definition":"Forme rare de maladie lysosomale qui se caractérise par une accumulation de sulfatides dans le système nerveux central et périphérique en raison d'un déficit de l'enzyme arylsulfatase A, entraînant une démyélinisation. En fonction de l'âge d'apparition des symptômes, on distingue trois sous-types cliniques de la maladie : infantile tardive, juvénile et adulte. Selon le sous-type, les principaux symptômes sont la détérioration des fonctions motrices ou cognitives ou des problèmes de comportement, le tout aboutissant finalement à un état décérébré et au décès après une évolution et une durée de la maladie très variables. La maladie se transmet selon le mode autosomique récessif."},"de":{"name":"Leukodystrophie, metachromatische","synonyms":["Arylsulfatase A-Mangel","MLD"],"definition":"Eine seltene lysosomale Erkrankung, die durch eine Anhäufung von Sulfatiden im zentralen und peripheren Nervensystem aufgrund eines Mangels des Enzyms Arylsulfatase A gekennzeichnet ist und zu einer Demyelinisierung führt. Je nach Alter des Ausbruchs können drei klinische Subtypen unterschieden werden: spätes Säuglingsalter, Jugendalter und Erwachsenenalter. Leitsymptome sind je nach Subtyp eine Verschlechterung der motorischen oder kognitiven Funktionen oder Verhaltensprobleme, die nach einem sehr unterschiedlichen Krankheitsverlauf und einer sehr unterschiedlichen Krankheitsdauer schließlich zu einem dezerebrierten Zustand und zum Tod führen. Der Vererbungsmodus ist autosomal-rezessiv."},"es":{"name":"Leucodistrofia metacromática","synonyms":["Deficiencia de arilsulfatasa A","MLD"],"definition":"Es una enfermedad lisosomal poco frecuente caracterizada por el acúmulo de sulfátidos en el sistema nervioso central y periférico debido a la deficiencia de la enzima arilsulfatasa A, que resulta en desmielinización. Se pueden distinguir tres subtipos clínicos según la edad de inicio: el infantil tardío, el juvenil y el adulto. Los síntomas principales son el deterioro de la función motora o cognitiva o los trastornos de conducta, dependiendo el subtipo, que finalmente conduce a un estado de descerebración y fallecimiento tras un curso y una duración de la enfermedad muy variables. El modo de herencia de la enfermedad es autosómico recesivo."},"it":{"name":"Leucodistrofia metacromatica","synonyms":["Deficit di arilsulfatasi A","MLD"],"definition":"Si tratta di una malattia lisosomiale rara, caratterizzata dall'accumulo di solfatidi nel sistema nervoso centrale e periferico, causato da un deficit dell'enzima arilsulfatasi A, che esita nella demielinizzazione. Esistono tre sottotipi clinici, che si distinguono per la diversa età d'esordio: tardo-infantile, giovanile e dell'adulto. I principali segni clinici sono il deterioramento della funzione motoria o cognitiva e i problemi comportamentali (a seconda del sottotipo), che esitano nella decerebrazione e nella morte dopo un decorso e una durata della malattia molto variabili. La trasmissione è autosomica recessiva."},"nl":{"name":"Metachromatische leukodystrofie","synonyms":["Arylsulfatase A-deficiëntie","MLD"],"definition":"Een zeldzame lysosomale aandoening, gekarakteriseerd door accumulatie van sulfatiden in centraal en perifeer zenuwstelsel als gevolg van deficiëntie van het enzym arylsulfatase A, wat leidt tot demyelinisatie. Op basis van aanvangsleeftijd kunnen drie subtypes onderscheiden worden: laat infantiel, juveniel, en volwassen. De voornaamste symptomen zijn aftakeling van motorische of cognitieve functie of gedragsproblemen, afhankelijk van het subtype, die allen uiteindelijk culmineren in decerebratie en sterfte na een hoogst variabel ziekteverloop en een zeer variabele duur van de ziekte. Overerving gebeurt autosomaal recessief."},"pt":{"name":"Leucodistrofia metacromática","synonyms":["Deficiência de arilsulfatase A"]},"pl":{"name":"Leukodystrofia metachromatyczna","synonyms":["MLD","Niedobór arylosulfatazy A"],"definition":"Rzadka choroba lizosomalna charakteryzująca się gromadzeniem się sulfatydów w ośrodkowym i obwodowym układzie nerwowym wskutek niedoboru enzymu arylosulfatazy A, co prowadzi do demielinizacji. W zależności od wieku zachorowania można wyróżnić trzy podtypy kliniczne: późnoniemowlęcy, młodzieńczy i osób dorosłych. W zależności od podtypu głównymi objawami są pogorszenie sprawności ruchowej i funkcji poznawczych oraz problemy behawioralne, Pomimo zróżnicowanego nasilenia objawów i czasu trwania choroba ostatecznie prowadzi do stanu odkorowania i śmierci. Sposób dziedziczenia - autosomalny recesywny."},"cs":{"name":"Metachromatická leukodystrofie","synonyms":["Deficit arylsulfatázy A","MLD"]},"uk":{"name":"Метахроматична лейкодистрофія","synonyms":["Дефіцит арилсульфатази А","MLD"],"definition":"A rare lysosomal disease characterized by accumulation of sulfatides in the central and peripheral nervous system due to deficiency of the enzyme arylsulfatase A, leading to demyelination. Three clinical subtypes can be distinguished based on the age of onset: late infantile, juvenile, and adult. Lead symptoms are deterioration in motor or cognitive function or behavioral problems, depending on the subtype, all eventually culminating in a decerebrated state and death after a highly variable disease course and duration. Mode of inheritance is autosomal recessive."},"zh":{"name":"异染性脑白质营养不良","synonyms":["芳香基硫酸酯酶A缺乏症"]},"tr":{"name":"Metakromatik lökodistrofi","synonyms":["MLD","Arilsülfataz A eksikliği"]}},"xrefs":[{"source":"OMIM","code":"156310","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"249900","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"250100","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E75.2","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5C56.02","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"172326564"},{"source":"MONDO","code":"0018868","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D007966","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0023522","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3230","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10067609","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":68356,"name":"Leukodystrophy","classifications":[156,181]},{"orpha":98543,"name":"Metabolic disease with dementia","classifications":[156,181]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":207018,"name":"Rare hereditary metabolic disease with peripheral neuropathy","classifications":[156,181]},{"orpha":79225,"name":"Sphingolipidosis","classifications":[150,156,233]},{"orpha":371442,"name":"Sphingolipidosis with epilepsy","classifications":[156,181]},{"orpha":441434,"name":"Syndromic hereditary optic neuropathy","classifications":[156,189]}],"children":[{"orpha":309271,"name":"Metachromatic leukodystrophy, adult form","type":"Clinical subtype"},{"orpha":309263,"name":"Metachromatic leukodystrophy, juvenile form","type":"Clinical subtype"},{"orpha":309256,"name":"Metachromatic leukodystrophy, late infantile form","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"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"],"via":{"orpha":309256,"name":"Metachromatic leukodystrophy, late infantile form"}},{"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"],"via":{"orpha":309263,"name":"Metachromatic leukodystrophy, juvenile form"}},{"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"],"via":{"orpha":309271,"name":"Metachromatic leukodystrophy, adult form"}},{"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"],"via":{"orpha":309256,"name":"Metachromatic leukodystrophy, late infantile form"}},{"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"],"via":{"orpha":309263,"name":"Metachromatic leukodystrophy, juvenile form"}},{"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"],"via":{"orpha":309271,"name":"Metachromatic leukodystrophy, adult form"}}],"inheritance":["Autosomal recessive"],"onset":["Adolescent","Adult","Childhood","Infancy"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.47,"area":"Europe","status":"Validated","source":"21496291[PMID]_[EXPERT]_European Medicines Agency 2010[OTHER]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.1,"area":"Europe","status":"Validated","source":"21496291[PMID]_[EXPERT]_European Medicines Agency 2010[OTHER]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.42,"area":"Netherlands","status":"Validated","source":"10480370[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.85,"area":"Portugal","status":"Validated","source":"14685153[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.6,"area":"Germany","status":"Validated","source":"9286459[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.43,"area":"Turkey","status":"Validated","source":"20490927[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.09,"area":"Australia","status":"Validated","source":"9918480[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.69,"area":"Czech Republic","status":"Validated","source":"20490927[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.38,"area":"Poland","status":"Validated","source":"21695197[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.73,"area":"Sweden","status":"Validated","source":"25274184[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":2.5,"area":"United States","status":"Validated","source":"19380076[PMID]"},{"type":"Prevalence at birth","qualification":"Class only","class":"1-9 / 100 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_21695197[PMID]_20490927[PMID]_19380076[PMID]_9918480[PMID]_9286459[PMID]_14685153[PMID]_10480370[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-03-09","source":"20301509[PMID]_25987178[PMID]_20571983[PMID]","terms":[{"hpo":"HP:0012379","label":"Abnormal enzyme/coenzyme activity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0006970","label":"Periventricular leukomalacia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000649","label":"Abnormality of visual evoked potentials","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"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:0008947","label":"Floppy infant","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002359","label":"Frequent falls","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030890","label":"Hyperintensity of cerebral white matter on MRI","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:0003394","label":"Muscle spasm","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009830","label":"Peripheral neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002191","label":"Progressive spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000505","label":"Visual impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030858","label":"Addictive behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002607","label":"Bowel incontinence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000726","label":"Dementia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000712","label":"Emotional lability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011471","label":"Gastrostomy tube feeding in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031064","label":"Impaired continence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002311","label":"Incoordination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009763","label":"Limb pain","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012531","label":"Pain","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000751","label":"Personality changes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000709","label":"Psychosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100753","label":"Schizophrenia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030051","label":"Tip-toe gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000020","label":"Urinary incontinence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012437","label":"Abnormal gallbladder morphology","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002577","label":"Abnormal stomach morphology","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002246","label":"Abnormality of the duodenum","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0025013","label":"Decerebrate rigidity","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0100762","label":"Hemobilia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002576","label":"Intussusception","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0100575","label":"Neoplasm of the gallbladder","frequency":"Very rare (<4-1%)","criteria":null}]}}