{"orpha":502444,"name":"Alkaline ceramidase 3 deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["ACER3-related early childhood-onset progressive leukodystrophy","Leukodystrophy due to alkaline ceramidase 3 deficiency"],"definition":"A rare genetic leukodystrophy characterized by infantile onset of stagnation and regression of motor and language development resulting in complete lack of communication and purposeful movement. Further neurological manifestations include truncal hypotonia, appendicular spasticity, dystonia, optic disc pallor, peripheral neuropathy, and neurogenic bladder. Patients also present multiple contractures, late-onset relative macrocephaly, short stature, and facial dysmorphism (including coarse facial features, sloping forehead, thick eyebrows, low-set ears, prominent nose, flat philtrum, and prominent lower lip). Brain imaging at advanced stages shows diffuse abnormal white matter signal and severe atrophy. Sural nerve biopsy reveals decreased myelination.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-502444/","orphanet_url":"https://www.orpha.net/en/disease/detail/502444","names":{"fr":{"name":"Déficit en céramidase alcaline 3","synonyms":["Déficit en alkaline ceramidase 3","Leucodystrophie par déficit en alkaline ceramidase 3","Leucodystrophie par déficit en céramidase alcaline 3","Leucodystrophie progressive associée à ACER3"],"definition":"Leucodystrophie rare d'origine génétique, caractérisée par l'apparition infantile d'une stagnation ou d'une régression du développement moteur et du langage, entraînant une absence totale de communication et de mouvements volontaires. Parmi les autres manifestations neurologiques figurent une hypotonie du tronc, une spasticité du squelette appendiculaire, une dystonie, une pâleur papillaire, une neuropathie périphérique et une vessie neurologique. Les patients présentent également de multiples contractures, une macrocéphalie relative à début tardif, une petite taille et une dysmorphie faciale (traits de visage grossiers, front fuyant, sourcils épais, oreilles d'implantation basse, nez proéminent, philtrum plat et lèvre inférieure proéminente). L'imagerie cérébrale à un stade avancé met en évidence une anomalie diffuse de signal de la substance blanche et une atrophie sévère. La biopsie du nerf sural révèle une diminution de la myélinisation."},"de":{"name":"Alkalische Ceramidase 3-Mangel","synonyms":["Leukodystrophie durch alkalische Ceramidase 3-Mangel","Leukodystrophie, progressive, mit Beginn in der frühen Kindheit, ACER3-assoziierte"],"definition":"Eine seltene genetisch bedingte Leukodystrophie, die durch eine Stagnation und Regression der motorischen und sprachlichen Entwicklung gekennzeichnet ist, die in der Kindheit beginnt und zu einem völligen Fehlen von Kommunikation und zielgerichteten Bewegungen führt. Weitere neurologische Manifestationen sind Hypotonie des Rumpfes, appendikuläre Spastizität, Dystonie, Blässe des Sehnervenkopfes, periphere Neuropathie und neurogene Harnblase. Die Patienten zeigen auch multiple Kontrakturen, späte relative Makrozephalie, Kleinwuchs und Gesichtsdysmorphien (einschließlich grober Gesichtszüge, schiefer Stirn, dicker Augenbrauen, tiefsitzender Ohren, hervorstehender Nase, flachem Philtrum und hervorstehender Unterlippe). Die zerebrale Bildgebung im fortgeschrittenen Stadium zeigt diffuse abnorme Signale der weißen Substanz und eine schwere Atrophie. Die Biopsie des Nervus suralis zeigt eine verminderte Myelinisierung."},"es":{"name":"Deficiencia de ceramidasa alcalina 3","synonyms":["Leucodistrofia por deficiencia de ceramidasa alcalina 3","Leucodistrofia progresiva de inicio en la infancia temprana asociada a ACER3"],"definition":"Es una leucodistrofia de origen genético poco frecuente caracterizada por detención y regresión del desarrollo motor y del lenguaje de inicio en la lactancia resultando en la ausencia total de la comunicación y del movimiento voluntario. Otras manifestaciones neurológicas son hipotonía troncal, espasticidad apendicular, distonía, palidez del disco óptico, neuropatía periférica y vejiga neurogénica. Los pacientes también presentan múltiples contracturas, macrocefalia relativa de inicio tardío, talla baja y dismorfia facial (incluyendo rasgos faciales toscos, frente inclinada, cejas espesas, orejas de implantación baja, nariz y labio inferior prominentes y filtrum plano). La neuroimagen muestra una señal difusa de sustancia blanca anómala y una grave atrofia en etapas avanzadas. La biopsia del nervio sural revela una disminución de la mielinización."},"it":{"name":"Deficit di ceramidasi alcalina 3","definition":"Si tratta di una leucodistrofia genetica rara, che esordisce nella prima infanzia con arresto e regressione dello sviluppo motorio e del linguaggio, esitando nell'assenza completa di comunicazione e di movimenti intenzionali. Altri sintomi neurologici sono l'ipotonia del tronco, la spasticità appendicolare, la distonia, il pallore del disco ottico, la neuropatia periferica e la vescica neurogena. I pazienti presentano anche contratture multiple, macrocefalia relativa ad esordio tardivo, bassa statura e dismorfismi facciali (aspetto grossolano del viso, fronte sfuggente, sopracciglia folte, orecchie a basso impianto, naso prominente, filtro piatto e labbro inferiore prominente). Negli stadi avanzati della malattia, le neuroimmagini evidenziano anomalie diffuse del segnale della sostanza bianca e atrofia marcata. La biopsia del nervo surale evidenzia una ridotta mielinizzazione."},"nl":{"name":"Alkalisch ceramidase 3-deficiëntie","synonyms":["ACER3-gerelateerde progressieve leukodystrofie met aanvang in de vroege kindertijd","Leukodystrofie als gevolg van alkalisch ceramidase 3-deficiëntie"],"definition":"Een zeldzame, genetische leukodystrofie, gekarakteriseerd door infantiele aanvang van stagnatie en regressie van motorische ontwikkeling en taalontwikkeling, wat resulteert in volledig gebrek aan communicatie en zinvolle beweging. Overige neurologische manifestaties zijn onder meer hypotonie van romp, appendiculaire spasticiteit, dystonie, bleekheid van optische papil, perifere neuropathie, en neurogene blaas. Patiënten vertonen ook multipele contracturen, laat optredende relatieve macrocefalie, kleine gestalte, en faciale dysmorfie (met onder meer ruwe gelaatstrekken, hellend voorhoofd, dikke wenkbrauwen, laagstaande oren, prominente neus, plat filtrum, en prominente onderlip). Beeldvorming van de hersenen in latere stadia toont diffuse abnormale signalen van witte stof en ernstige atrofie. Biopsie van nervus suralis toont verminderde myelinisatie."},"pt":{"name":"Deficiência de ceramidase 3 alcalina"},"pl":{"name":"Niedobór ceramidazy alkalicznej 3","synonyms":["Lekodystrofia z powodu niedoboru ceramidazy alkalinowej 3"]},"cs":{"name":"Deficit alkalické ceramidázy 3","synonyms":["Leukodystrophy due to alkaline ceramidase 3 deficiency","ACER3-related early childhood-onset progressive leukodystrophy","Leukodystrofie způsobená deficitem alkalické ceramidázy 3","Progresivní leukodystrofie v raném dětství související s ACER3"]},"uk":{"name":"Дефіцит лужної церамідази 3","synonyms":["ACER3-асоційована прогресуюча лейкодистрофія, що починається в ранньому дитячому віці","Лейкодистрофія внаслідок дефіциту лужної церамідази 3"],"definition":"A rare genetic leukodystrophy characterized by infantile onset of stagnation and regression of motor and language development resulting in complete lack of communication and purposeful movement. Further neurological manifestations include truncal hypotonia, appendicular spasticity, dystonia, optic disc pallor, peripheral neuropathy, and neurogenic bladder. Patients also present multiple contractures, late-onset relative macrocephaly, short stature, and facial dysmorphism (including coarse facial features, sloping forehead, thick eyebrows, low-set ears, prominent nose, flat philtrum, and prominent lower lip). Brain imaging at advanced stages shows diffuse abnormal white matter signal and severe atrophy. Sural nerve biopsy reveals decreased myelination."},"zh":{"name":"碱性神经酰胺酶3缺陷","synonyms":["ACER3相关的儿童早期发病的进行性脑白质营养不良症"]},"tr":{"name":"Alkali seramidaz 3 eksikliği","synonyms":["Alkalin seramidaz 3 eksikliğine bağlı lökodistrofi","ACER3-ilişkili erken çocukluk dönemi başlangıçlı ilerleyici lökodistrofi"]}},"xrefs":[{"source":"OMIM","code":"617762","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E75.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0044718","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4540358","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":68385,"name":"Neurometabolic disease","classifications":[156,181]}],"children":[],"genes":[{"symbol":"ACER3","name":"alkaline ceramidase 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26792856[PMID]","hgnc":"16066","ensembl":"ENSG00000078124","omim":"617036","loci":["11q13.5"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"26792856[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26792856[PMID]"}],"phenotypes":null}