{"orpha":404454,"name":"Alacrimia-choreoathetosis-liver dysfunction syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["NGLY1 deficiency","NGLY1-CDDG"],"definition":"A rare, genetic, inborn error of metabolism disorder characterized by global developmental delay, hypotonia, choreoathetosis, hypo-/alacrimia, and liver dysfunction which manifests with elevated liver transaminases and hepatocyte cytoplasmic storage material or vacuolization on liver biopsy. Additional features reported include acquired microcephaly, hypo-/areflexia, seizures, peripheral neuropathy, intellectual and language/speech disability, additional ocular anomalies and EEG and brain imaging abnomalities.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-404454/","orphanet_url":"https://www.orpha.net/en/disease/detail/404454","names":{"fr":{"name":"Syndrome d'alacrymie-choréoathétose-hépatopathie","synonyms":["Déficit en NGLY1","NGLY1-CDDG"],"definition":"Erreur innée du métabolisme rare, d'origine génétique, caractérisée par un retard de développement global, une hypotonie, une choréoathétose, une hypo-/alacrymie et une hépatopathie qui se manifeste par des taux élevés de transaminases hépatiques et par la présence, observée à la biopsie hépatique, de matériel ou de vacuoles de stockage dans la membrane cytoplasmique des hépatocytes. Les autres signes rapportés comprennent une microcéphalie acquise, une hypo-/aréflexie, des crises convulsives, une neuropathie périphérique, une déficience intellectuelle et un retard de langage/parole, d'autres anomalies oculaires, ainsi que des anomalies visibles à l'EEG et à l'imagerie cérébrale."},"de":{"name":"Alakrimie-Choreoathetose-Leberdysfunktion-Syndrom","synonyms":["NGLY1-CDDG","NGLY1-Mangel"]},"es":{"name":"Síndrome de alacrimia-coreoatetosis-disfunción hepática","synonyms":["Deficiencia de NGLY1","NGLY1-CDDG"],"definition":"Es un error innato del metabolismo, genético y poco frecuente, caracterizado por retraso global del desarrollo, hipotonía, coreoatetosis, hipo/alacrimia y disfunción hepática, que se manifiesta con transaminasas hepáticas elevadas y presencia de material de almacenamiento citoplasmático o vacuolización en hepatocitos en biopsias hepáticas. Otras características adicionales descritas incluyen microcefalia adquirida, hipo/arreflexia, convulsiones, neuropatía periférica, discapacidad intelectual y del habla/lenguaje, anomalías oculares adicionales y anomalías en el EEG y en estudios de neuroimagen."},"it":{"name":"Sindrome da alacrimia, coreoatetosi e disfunzione epatica","synonyms":["Deficit di NGLY1","NGLY1-CDDG"],"definition":"La sindrome che associa l'alacrimia, la coreoatetosi e la disfunzione epatica è un errore congenito raro del metabolismo, di origine genetica, caratterizzato da ritardo dello sviluppo globale, ipotonia, coreoatetosi, ipo-/alacrimia e disfunzione renale, che esordisce con un aumento dei valori delle transaminasi epatiche. La biopsia del fegato evidenzia un accumulo di materiale nel citoplasma degli epatociti o la loro vacuolizzazione. Altri segni clinici sono la microcefalia acquisita, l'ipo-/areflessia, le crisi epilettiche, la neuropatia periferica, la disabilità intellettiva e i difetti del linguaggio, le anomalie oculari e dell'EEG e delle neuroimmagini."},"nl":{"name":"Alacrimie - choreoathetose - leverdisfunctie-syndroom","synonyms":["NGLY1-CDDG","NGLY1-deficiëntie"],"definition":"Een zeldzame, genetische, aangeboren stofwisselingsziekte, gekarakteriseerd door algehele ontwikkelingsachterstand, hypotonie, choreoathetose, hypo-/alacrimie, en leverdisfunctie die zich manifesteert met verhoogde transaminasen in de lever en opslag van materiaal of vacuolisatie in cytoplasma van hepatocyten bij leverbiopsie. Bijkomende kenmerken die werden gerapporteerd, zijn onder meer verworven microcefalie, hypo-/areflexie, insulten, perifere neuropathie, intellectuele en taal-/spraakachterstand, bijkomende oculaire anomalieën en afwijkingen bij EEG en beeldvorming van de hersenen."},"pt":{"name":"Síndrome de alacrimia - coreoatetose - disfunção hepática"},"pl":{"name":"Zespół braku łez, choreoatetozy i dysfunkcji wątroby","synonyms":["NGLY1-CDDG","Niedobór NGLY1"]},"cs":{"name":"Syndrom zahrnující alakrimii, choreoatetózu a dysfukci jater","synonyms":["Deficit NGLY1","NGLY1-CDDG"]},"uk":{"name":"Синдром алакрімії-хореоатетозу-печінкової дисфункції","synonyms":["Дефіцит NGLY1","NGLY1-CDDG"],"definition":"A rare, genetic, inborn error of metabolism disorder characterized by global developmental delay, hypotonia, choreoathetosis, hypo-/alacrimia, and liver dysfunction which manifests with elevated liver transaminases and hepatocyte cytoplasmic storage material or vacuolization on liver biopsy. Additional features reported include acquired microcephaly, hypo-/areflexia, seizures, peripheral neuropathy, intellectual and language/speech disability, additional ocular anomalies and EEG and brain imaging abnomalities."},"zh":{"name":"无泪-舞蹈手足徐动症-肝功能障碍综合征","synonyms":["NGLY1缺乏"],"definition":"一种罕见的遗传性先天性代谢障碍，其特征在于全面发育延迟，肌张力低下，胆囊炎，嗅觉减弱或嗅觉过敏和肝功能障碍，表现为转氨酶升高、肝脏活检提示肝脏细胞胞质堆积和空泡化。报告的其他特征包括获得性小头畸形，反射亢进或减弱，癫痫发作，周围神经病，智力和语言障碍，其他眼部异常，脑电图和脑成像异常。"},"tr":{"name":"Alakrimia-koreoatetoz-karaciğer disfonksiyon sendromu","synonyms":["NGLY1-CDDG","NGLY1 deksikliği"]}},"xrefs":[{"source":"OMIM","code":"615273","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E77.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C54.Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0800044","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C000626124","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C3808991","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"12315","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93626,"name":"Rare renal disease"},"parents":[{"orpha":281244,"name":"Autosomal ichthyosis syndrome with other associated signs","classifications":[156,187]},{"orpha":98604,"name":"Congenital alacrima","classifications":[156,189]},{"orpha":183484,"name":"Genetic subcutaneous tissue disorder","classifications":[156]},{"orpha":91088,"name":"Other metabolic disease","classifications":[150,156]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]},{"orpha":79382,"name":"Subcutaneous tissue disease","classifications":[187]}],"children":[],"genes":[{"symbol":"NGLY1","name":"N-glycanase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"24651605[PMID]","hgnc":"17646","ensembl":"ENSG00000151092","omim":"610661","loci":["3p24.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":8.0,"area":"Worldwide","status":"Validated","source":"24651605[PMID]_22581936[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_24651605[PMID]_22581936[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-07-12","source":"31217022[PMID]_27388694[PMID]_24651605[PMID]_29419975[PMID]","terms":[{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002487","label":"Hyperkinetic movements","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007141","label":"Sensorimotor neuropathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012447","label":"Abnormal myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000522","label":"Alacrima","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001266","label":"Choreoathetosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012450","label":"Chronic constipation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025455","label":"Decreased CSF 5-hydroxyindolacetic acid concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025458","label":"Decreased CSF albumin","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040209","label":"Decreased CSF biopterin level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003785","label":"Decreased CSF homovanillic acid concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025457","label":"Decreased CSF protein","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003563","label":"Decreased LDL cholesterol concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000633","label":"Decreased lacrimation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002123","label":"Generalized myoclonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012153","label":"Hypotriglyceridemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002659","label":"Increased susceptibility to fractures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002187","label":"Intellectual disability, profound","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002870","label":"Obstructive sleep apnea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001518","label":"Small for gestational age","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001771","label":"Achilles tendon contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003086","label":"Acromesomelia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002345","label":"Action tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0020037","label":"Astasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002305","label":"Athetosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010819","label":"Atonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003447","label":"Axonal loss","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002072","label":"Chorea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001374","label":"Congenital hip dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000559","label":"Corneal scarring","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002673","label":"Coxa valga","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012340","label":"Decreased resting energy expenditure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025336","label":"Delayed ability to sit","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000297","label":"Facial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030194","label":"Fatigable weakness of speech muscles","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010821","label":"Focal emotional seizure with laughing","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011167","label":"Focal tonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002909","label":"Generalized aminoaciduria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002121","label":"Generalized non-motor (absence) seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002171","label":"Gliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001385","label":"Hip dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011900","label":"Hypofibrinogenemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031146","label":"Impaired oral bolus formation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031162","label":"Impaired oropharyngeal swallow response","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003121","label":"Limb joint contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031008","label":"Lingual dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001413","label":"Micronodular cirrhosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001414","label":"Microvesicular hepatic steatosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001336","label":"Myoclonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011954","label":"Nodular regenerative hyperplasia of liver","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000657","label":"Oculomotor apraxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008151","label":"Prolonged prothrombin time","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002205","label":"Recurrent respiratory infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004349","label":"Reduced bone mineral density","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001929","label":"Reduced factor XI activity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005543","label":"Reduced protein C activity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100899","label":"Sclerosis of finger phalanx","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005484","label":"Secondary microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003834","label":"Shoulder dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001744","label":"Splenomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025401","label":"Staring gaze","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030906","label":"Suck reflex","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031051","label":"Tarsal sclerosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001488","label":"Bilateral ptosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000548","label":"Cone/cone-rod dystrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0011496","label":"Corneal neovascularization","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000577","label":"Exotropia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0030001","label":"Lagophthalmos","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000543","label":"Optic disc pallor","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000580","label":"Pigmentary retinopathy","frequency":"Very rare (<4-1%)","criteria":null}]}}