{"orpha":71278,"name":"Congenital brain dysgenesis due to glutamine synthetase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Inherited GS deficiency","Inherited glutamine synthetase deficiency"],"definition":"A rare neurometabolic disease characterized by neonatal onset of severe epileptic encephalopathy with brain malformations (including cerebral and cerebellar atrophy, white matter abnormalities, delayed gyration or complete agyria, and thin corpus callosum), generalized hypotonia, and lack of normal development. Additional features include facial dysmorphism and necrolytic erythema of the skin. Biochemical hallmarks are decreased levels of glutamine in body fluids and chronic hyperammonemia. Death may occur in the early post-natal period due to multiple organ failure.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-71278/","orphanet_url":"https://www.orpha.net/en/disease/detail/71278","names":{"fr":{"name":"Dysgénésie cérébrale congénitale par déficit en glutamine synthétase","synonyms":["Déficit héréditaire en GS","Déficit héréditaire en glutamine synthétase"],"definition":"Maladie neurométabolique rare caractérisée par l'apparition néonatale d'une encéphalopathie épileptique sévère avec des malformations cérébrales (notamment une atrophie cérébrale et cérébelleuse, des anomalies de la substance blanche, un retard de la gyration ou agyrie complète, et corps calleux court), une hypotonie généralisée et l'absence de développement. Les signes cliniques sont la dysmorphie faciale et l'érythème nécrolytique de la peau. Les signes biochimiques distinctifs sont une diminution des niveaux de glutamine dans les fluides corporels et une hyperammonémie chronique. Le décès peut survenir dans la période postnatale précoce en raison de la défaillance de plusieurs organes."},"de":{"name":"Hirnfehlbildung, kongenitale, durch Glutamin-Synthetase-Mangel","synonyms":["Glutamin-Synthetase-Mangel, kongenitaler"],"definition":"Eine seltene neurometabolische Erkrankung, die durch eine schwere epileptische Enzephalopathie im Neugeborenenalter mit Fehlbildungen des Gehirns (einschließlich zerebraler und zerebellärer Atrophie, Anomalien der weißen Substanz, verzögerter Gyration oder vollständiger Agyrien und dünnem Corpus callosum), generalisierter Hypotonie und dem Fehlen einer normalen Entwicklung gekennzeichnet ist. Weitere Merkmale sind Gesichtsdysmorphien und nekrolytische Erytheme der Haut. Biochemische Merkmale sind erniedrigte Glutaminwerte in den Körperflüssigkeiten und chronische Hyperammonämie. Der Tod kann in der frühen postnatalen Phase aufgrund von Multiorganversagen eintreten."},"es":{"name":"Disgenesia cerebral congénita por deficiencia de glutamina sintetasa","synonyms":["Deficiencia de GS hereditario","Deficiencia de glutamina sintetasa hereditaria","Deficiencia hereditaria de GS","Deficiencia hereditaria de glutamina sintetasa"],"definition":"Es una enfermedad neurometabólica poco frecuente caracterizada por el inicio neonatal de una encefalopatía epiléptica grave acompañada de malformaciones cerebrales (incluyendo atrofia cerebral y cerebelosa, alteraciones de la sustancia blanca, patrón giral simplificado o agiria completa y adelgazamiento del cuerpo calloso), hipotonía generalizada y ausencia de un desarrollo normal. Otros hallazgos adicionales incluyen dismorfia facial y eritema cutáneo necrolítico. Las características bioquímicas distintivas de la enfermedad son unos niveles reducidos de glutamina en los líquidos biológicos y la hiperamonemia crónica. Puede ocurrir un fallecimiento en el período postnatal temprano debido a un fallo multiorgánico."},"it":{"name":"Disgenesia cerebrale congenita da deficit di glutammina sintetasi","synonyms":["Deficit ereditario di GS","Deficit ereditario di glutamina sintetasi"],"definition":"Si tratta di una malattia neurometabolica rara, che esordisce in epoca neonatale con encefalopatia epilettica grave associata a malformazioni cerebrali (atrofia cerebrale e cerebellare, anomalie della sostanza bianca, ritardo delle circonvoluzioni o agiria completa e assottigliamento del corpo calloso), ipotonia generalizzata e anomalie dello sviluppo. Altri segni clinici sono i dismorfismi facciali e l'eritema cutaneo necrolitico. Gli esami biochimici evidenziano una diminuzione dei livelli di glutammina nei liquidi corporei e iperammoniemia cronica. I pazienti muoiono poco dopo la nascita a causa dell'insufficienza multiorgano."},"nl":{"name":"Congenitale dysgenesie van hersenen door deficiëntie van glutaminesynthetase","synonyms":["Erfelijke GS-deficiëntie","Erfelijke deficiëntie van glutaminesynthetase"],"definition":"Een zeldzame neurometabole aandoening, gekarakteriseerd door neonatale aanvang van ernstige epileptische encefalopathie met hersenmalformaties (waaronder cerebrale en cerebellaire atrofie, afwijkingen van witte stof, vertraagde gyratie of volledige agyrie, en dun corpus callosum), gegeneraliseerde hypotonie, en gebrek aan normale ontwikkeling. Bijkomende kenmerken zijn onder meer faciale dysmorfie en necrolytisch erytheem van huid. Biochemische kenmerken zijn verlaagde gehaltes van glutamine in lichaamsvloeistoffen en chronische hyperammoniëmie. Overlijden kan optreden in de vroege postnatale periode als gevolg van multiorgaanfalen."},"pt":{"name":"Disgenesia cerebral congénita por deficiência de glutamina sintetase"},"pl":{"name":"Wrodzona dysgenezja mózgu spowodowana niedoborem syntetazy glutaminy","synonyms":["Dziedziczny Niedobór GS","Dziedziczny Niedobór syntetazy glutaminy"]},"cs":{"name":"Vrozená dysgeneze mozku způsobená deficitem glutamin syntetázy","synonyms":["Dědičný deficit GS","Dědičný deficit glutaminsyntetázy"]},"uk":{"name":"Вроджена дисгенезія головного мозку внаслідок дефіциту глутамінсинтетази","synonyms":["Спадковий дефіцит глутамінсинтетази","Спадковий дефіцит ГС"],"definition":"A rare neurometabolic disease characterized by neonatal onset of severe epileptic encephalopathy with brain malformations (including cerebral and cerebellar atrophy, white matter abnormalities, delayed gyration or complete agyria, and thin corpus callosum), generalized hypotonia, and lack of normal development. Additional features include facial dysmorphism and necrolytic erythema of the skin. Biochemical hallmarks are decreased levels of glutamine in body fluids and chronic hyperammonemia. Death may occur in the early post-natal period due to multiple organ failure."},"zh":{"name":"谷氨酰胺合成酶缺乏所致脑发育不全","synonyms":["遗传性谷氨酰胺合成酶缺乏症"]},"tr":{"name":"Glutamin sentetaz eksikliğine bağlı doğumsal beyin disgenezi","synonyms":["Kalıtsal GS eksikliği","Kalıtsal glutamin sentetaz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"610015","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E72.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C50.Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"238162640"},{"source":"MONDO","code":"0012393","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5680112","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"9848","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":289841,"name":"Disorder of glutamine metabolism","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"GLUL","name":"glutamate-ammonia ligase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"16267323[PMID]","hgnc":"4341","ensembl":"ENSG00000135821","omim":"138290","loci":["1q25.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":3.0,"area":"Worldwide","status":"Validated","source":"21353613[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_21353613[PMID]"}],"phenotypes":null}