{"orpha":445038,"name":"3-methylglutaconic aciduria-neonatal cataract-neurologic involvement-congenital neutropenia syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["3-methylglutaconic aciduria type 7","MGA-neonatal cataract-neurologic involvement-congenital neutropenia syndrome","MGA7"],"definition":"A rare organic aciduria characterized by increased urinary excretion of 3-methylglutaconic acid, variably associated with neutropenia (sometimes causing recurrent severe infections and potentially resulting in leukemia) and progressive neurologic manifestations, such as global developmental delay, intellectual disability, hypotonia, movement disorder, and seizures. Microcephaly, cataract, facial dysmorphism, growth retardation, endocrine abnormalities, and cardiomyopathy have also been reported. Brain imaging may show cerebral or cerebellar atrophy, or abnormalities of the basal ganglia.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-445038/","orphanet_url":"https://www.orpha.net/en/disease/detail/445038","names":{"fr":{"name":"Syndrome de cataracte néonatale-atteinte neurologique-neutropénie congénitale-acidurie 3-méthylglutaconique","synonyms":["AMG7","Acidurie 3-méthylglutaconique type 7","MGA7","Syndrome de cataracte néonatale-atteinte neurologique-neutropénie congénitale-AMG","Syndrome de cataracte néonatale-atteinte neurologique-neutropénie congénitale-MGA"],"definition":"Acidurie organique rare caractérisée par une excrétion urinaire accrue d'acide 3&nbsp;-&nbspméthylglutaconique, variablement associée à une neutropénie (provoquant parfois des infections récurrentes sévères et pouvant aboutir à une leucémie) et à des signes cliniques neurologiques progressifs, telles qu'un retard de développement global, une déficience intellectuelle, une hypotonie, des troubles du mouvement et des crises convulsives. Une microcéphalie, une cataracte, une dysmorphie faciale, un retard de croissance, des anomalies endocriniennes et une cardiomyopathie ont également été rapportés. L'imagerie cérébrale peut révéler une atrophie cérébrale ou cérébelleuse, ou des malformations des ganglions de la base."},"de":{"name":"3-Methylglutaconazidurie-Katarakt-neurologische Beteiligung-Neutropenie-Syndrom","synonyms":["3-Methylglutaconazidurie Typ 7","MGA-neonataler Katarakt-neurologische Beteiligung-kongenitale Neutropenie-Syndrom","MGA7"],"definition":"Eine seltene organische Azidurie, die durch eine erhöhte Ausscheidung von 3-Methylglutaconsäure im Urin gekennzeichnet ist und mit Neutropenie (die manchmal wiederkehrende schwere Infektionen verursacht und zu Leukämie führen kann) und progressiven neurologischen Manifestationen wie globaler Entwicklungsverzögerung, Intelligenzminderung, Hypotonie, Bewegungsstörungen und Krampfanfällen einhergehen kann. Es wurde auch über Mikrozephalie, Katarakt, Gesichtsdysmorphien, Wachstumsverzögerung, endokrine Anomalien und Kardiomyopathie berichtet. Die Bildgebung des Gehirns kann eine zerebrale oder zerebellare Atrophie oder Anomalien der Basalganglien zeigen."},"es":{"name":"Síndrome de aciduria 3-metilglutacónica-catarata neonatal-afectación neurológica-neutropenia congénita","synonyms":["Aciduria 3-metilglutacónica tipo 7","MGA7","Síndrome MGA-catarata neonatal-afectación neurológica-neutropenia congénita"],"definition":"Es una aciduria orgánica poco frecuente caracterizada por un aumento de la excreción urinaria de ácido 3-metilglutacónico, asociado de forma variable a neutropenia (causando en ocasiones infecciones graves recurrentes que pueden resultar en leucemia) y manifestaciones neurológicas progresivas, tales como retraso global del desarrollo, discapacidad intelectual, hipotonía, trastornos del movimiento, y crisis epilépticas. También se ha descrito microcefalia, cataratas, dismorfia facial, retraso del crecimiento, anomalías endocrinas y miocardiopatía. La neuroimagen puede mostrar atrofia cerebral o cerebelosa o anomalías de los ganglios basales."},"it":{"name":"Sindrome aciduria 3 metilglutaconica-cataratta neonatale-interessamneto neurologico-neutropenia congenita","synonyms":["Aciduria 3-metilglutaconica, tipo 7","MGA7","Sindrome MGA-cataratta neonatale-interessamneto neurologico-neutropenia congenita"],"definition":"Si tratta di un'aciduria organica rara, caratterizzata da un aumento dell'acido 3-metilglutaconico nelle urine, che si associa in maniera variabile alla neutropenia (che talvolta causa infezioni gravi ricorrenti e può esitare nella leucemia) e a sintomi neurologici progressivi, che comprendono il ritardo dello sviluppo globale, la disabilità intellettiva, l'ipotonia, le anomalie del movimento e le crisi epilettiche. I pazienti possono presentare anche microcefalia, cataratta, dismorfismi facciali, ritardo della crescita, anomalie endocrine e cardiomiopatia. Le neuroimmagini evidenziano atrofia cerebrale o cerebellare, o anomalie dei gangli basali."},"nl":{"name":"3-methylglutaconacidurie - neonataal cataract - neurologische betrokkenheid - congenitale neutropenie-syndroom","synonyms":["3-methylglutaconacidurie type 7","MGA - neonataal cataract - neurologische betrokkenheid - congenitale neutropenie-syndroom","MGA7"],"definition":"Een zeldzame organische acidurie, gekarakteriseerd door verhoogde excretie van 3-methylglutaconzuur in urine, variabel geassocieerd met neutropenie (die soms recidiverende ernstige infecties veroorzaakt en mogelijk resulteert in leukemie) en progressieve neurologische manifestaties, zoals algehele ontwikkelingsachterstand, intellectuele achterstand, hypotonie, bewegingsstoornis, en insulten. Microcefalie, cataract, faciale dysmorfie, groeiretardatie, endocriene afwijkingen, en cardiomyopathie werden ook reeds gerapporteerd. Beeldvorming van hersenen toont mogelijk cerebrale of cerebellaire atrofie, of afwijkingen van basale ganglia."},"pt":{"name":"Síndrome de acidúria 3-metilglutacónica-catarata neonatal-envolvimento neurológico-neutropenia congénita","synonyms":["Acidúria 3-metilglutacónica tipo 7","MGA7","Síndrome MGA-catarata neonatal-envolvimento neurológico-neutropenia congénita"]},"pl":{"name":"Zespół kwasicy 3-metyloglutakonowej, zaćmy noworodkowej, zaburzeń neurologicznych oraz wrodzonej neutropenii","synonyms":["MGA7","Zespół acydurii 3-metyloglutakonowej, zaćmy, zaburzeń neurologicznych i neutropenii"]},"cs":{"name":"3-methylglutakonová acidurie, typ 7","synonyms":["Syndrom zahrnující 3-methylglutakonovou acidurii, kataraktu, neurologickou poruchu a neutropenii","MGA7"]},"uk":{"name":"Синдром 3-метилглутаконової ацидурії-неонатальної катаракти-неврологічних уражень-вродженої нейтропенії","synonyms":["3-метилглутаконова ацидурія типу 7","MGA7","Синдром МГА - неонатальна катаракта - неврологічне ураження - вродженаї нейтропенія"],"definition":"A rare organic aciduria characterized by increased urinary excretion of 3-methylglutaconic acid, variably associated with neutropenia (sometimes causing recurrent severe infections and potentially resulting in leukemia) and progressive neurologic manifestations, such as global developmental delay, intellectual disability, hypotonia, movement disorder, and seizures. Microcephaly, cataract, facial dysmorphism, growth retardation, endocrine abnormalities, and cardiomyopathy have also been reported. Brain imaging may show cerebral or cerebellar atrophy, or abnormalities of the basal ganglia."},"zh":{"name":"3-甲基戊酸尿症7型","synonyms":["3-甲基谷氨酸酸尿症-白内障-神经系统受累-中性粒细胞减少综合征"]},"tr":{"name":"3-metilglutakonik asidüri tip 7","synonyms":["MGA7","3-metilglutakonik asidüri-katarakt-nörolojik tutulum-nötropeni sendromu"]}},"xrefs":[{"source":"OMIM","code":"616271","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"619835","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E71.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C50.E0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"14561","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4225393","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":289902,"name":"3-methylglutaconic aciduria","classifications":[150,156]},{"orpha":98644,"name":"Metabolic disease with cataract","classifications":[156,189]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]},{"orpha":331184,"name":"Syndrome with congenital neutropenia as a major feature","classifications":[156,195,233]}],"children":[],"genes":[{"symbol":"CLPB","name":"ClpB family mitochondrial disaggregase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"25597511[PMID]_25597510[PMID]","hgnc":"30664","ensembl":"ENSG00000162129","omim":"616254","loci":["11q13.4"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":22.0,"area":"Worldwide","status":"Validated","source":"25650066[PMID]_25597511[PMID]_25597510[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_25650066[PMID]_25597511[PMID]_25597510[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-04-24","source":"25595726[PMID]_25597511[PMID]_25597510[PMID]","terms":[{"hpo":"HP:0003535","label":"3-Methylglutaconic aciduria","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000518","label":"Cataract","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001875","label":"Decreased total neutrophil count","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000121","label":"Nephrocalcinosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011451","label":"Primary microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000107","label":"Renal cyst","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002134","label":"Abnormal basal ganglia morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002071","label":"Abnormality of extrapyramidal motor function","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005528","label":"Bone marrow hypocellularity","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:0001266","label":"Choreoathetosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002194","label":"Delayed gross motor development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0410256","label":"Infection associated neutropenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001336","label":"Myoclonus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002179","label":"Opisthotonus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007153","label":"Progressive extrapyramidal movement disorder","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001638","label":"Cardiomyopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001397","label":"Hepatic steatosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000821","label":"Hypothyroidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001998","label":"Neonatal hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000083","label":"Renal insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002107","label":"Pneumothorax","frequency":"Very rare (<4-1%)","criteria":null}]}}