{"orpha":541423,"name":"Growth delay-intellectual disability-hepatopathy syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare, genetic, syndromic intellectual disability disease characterized by severe intrauterine and post-natal growth delay, moderate to severe intellectual disability, and neonatal-onset hepatopathy with fibrosis, steatosis, and/or cholestasis, occasionally leading to liver failure. Additional variable manifestations include muscular hypotonia, zinc deficiency, recurrent infections, diabetes mellitus, joint contractures, skin and joint laxity, hypervitaminosis D, and sensorineural hearing loss.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-541423/","orphanet_url":"https://www.orpha.net/en/disease/detail/541423","names":{"fr":{"name":"Syndrome de retard de croissance-déficience intellectuelle-hépatopathie","definition":"Déficience intellectuelle syndromique rare d'origine génétique caractérisée par un retard de croissance intra-utérin et post-natal, une déficience intellectuelle modérée à sévère et une hépatopathie à début néonatal avec fibrose, stéatose et/ou cholestase, pouvant mener à une insuffisance hépatique. Les autres manifestations, inconstantes, sont une hypotonie musculaire, une carence en fer, des infections récurrentes, un diabète sucré, des contractures articulaires, une laxité cutanée et articulaire, une hypervitaminose D et une surdité neurosensorielle."},"de":{"name":"Wachstumsverzögerung-Intelligenzminderung-Hepatopathie-Syndrom","definition":"Eine seltene, genetisch bedingte, syndromale Erkrankung mit intellektueller Entwicklungsstörung, die durch eine schwere intrauterine und postnatale Wachstumsverzögerung, eine mäßige bis schwere Intelligenzminderung und eine neonatale Hepatopathie mit Fibrose, Steatose und/oder Cholestase gekennzeichnet ist, die gelegentlich zu Leberversagen führt. Weitere variable Manifestationen sind Muskelhypotonie, Zinkmangel, rezidivierende Infektionen, Diabetes mellitus, Gelenkkontrakturen, Haut- und Gelenklaxität, Hypervitaminose D und sensorineurale Schwerhörigkeit."},"es":{"name":"Síndrome de retraso del crecimiento-discapacidad intelectual-hepatopatía","definition":"Es una discapacidad intelectual sindrómica, de origen genético y poco frecuente, caracterizada por un grave retraso en el crecimiento intrauterino y post-natal, discapacidad intelectual de moderada a profunda y hepatopatía de inicio neonatal con fibrosis, esteatosis y/o colestasis, que evolucionan ocasionalmente a insuficiencia hepática. Otras manifestaciones variables asociadas incluyen hipotonía muscular, deficiencia de zinc, infecciones recurrentes, diabetes mellitus, contracturas articulares, hiperlaxitud cutánea y articular, hipervitaminosis D e hipoacusia neurosensorial."},"it":{"name":"Sindrome da ritardo di crescita-disabilità intellettiva-epatopatia","definition":"Si tratta di una disabilità intellettiva sindromica rara, di origine genetica, caratterizzata da grave ritardo della crescita pre- e postnatale, disabilità intellettiva moderata-grave, ed epatopatia ad esordio neonatale associata a fibrosi, steatosi e/o colestasi, che occasionalmente esita nell'insufficienza epatica. Altri segni clinici variabili sono l'ipotonia muscolare, il deficit di zinco, le infezioni ricorrenti, il diabete mellito, le contratture articolari, la lassità cutanea e articolare, l'eccesso di vitamina D e la sordità neurosensoriale."},"nl":{"name":"Groeiachterstand - intellectuele achterstand - hepatopathie-syndroom","definition":"Een zeldzame, genetische, syndromale intellectuele achterstand gekarakteriseerd door ernstige intra-uteriene en postnatale groeiretardatie, matige tot ernstige intellectuele achterstand, en neonataal aanvangende hepatopathie met fibrose, steatose en/of cholestase, occasioneel met leverfalen tot gevolg. Bijkomende variabele manifestaties zijn onder meer musculaire hypotonie, zinkdeficiëntie, recurrente infecties, diabetes mellitus, gewrichtscontracturen, huid- en gewrichtslaxiteit, hypervitaminose D, en sensorineuraal gehoorverlies."},"pt":{"name":"Síndrome de atraso do crescimento-perturbação do desenvolvimento intelectual-hepatopatia"},"pl":{"name":"Zespół opóźnionego wzrastania, niepełnosprawności intelektualnej oraz hepatopatii"},"cs":{"name":"Syndrom zahrnující opoždění vývoje, mentální retardaci a hepatopatii"},"uk":{"name":"Синдром затримки росту-інтелектуальної недостатності-гепатопатії","definition":"A rare, genetic, syndromic intellectual disability disease characterized by severe intrauterine and post-natal growth delay, moderate to severe intellectual disability, and neonatal-onset hepatopathy with fibrosis, steatosis, and/or cholestasis, occasionally leading to liver failure. Additional variable manifestations include muscular hypotonia, zinc deficiency, recurrent infections, diabetes mellitus, joint contractures, skin and joint laxity, hypervitaminosis D, and sensorineural hearing loss."},"zh":{"name":"生长延迟-智力障碍-肝病综合征","definition":"一种罕见的遗传性综合征性智力障碍疾病，其特征是严重的宫内和产后生长发育迟缓，中度至重度智力障碍，以及新生儿期肝病，伴有纤维化、脂肪变性和（或）胆汁淤积，偶尔会导致肝衰竭。其他易变的表现包括肌张力低下、缺锌、反复感染、糖尿病、关节挛缩、皮肤和关节松弛、维生素D过多症和感音神经性听力损失。"},"tr":{"name":"Büyüme geriliği-zihinsel yetersizlik-hepatopati sendromu"}},"xrefs":[{"source":"OMIM","code":"617093","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"K76.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014911","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5568558","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":156604,"name":"Genetic parenchymatous liver disease","classifications":[156]},{"orpha":101939,"name":"Rare parenchymal liver disease","classifications":[183]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"IARS1","name":"isoleucyl-tRNA synthetase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"27426735[PMID]_29052218[PMID]","hgnc":"5330","ensembl":"ENSG00000196305","omim":"600709","loci":["9q22.31"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":6.0,"area":"Worldwide","status":"Validated","source":"29052218[PMID]_30431579[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_29052218[PMID]_30431579[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-08-18","source":"29052218[PMID]_27426735[PMID]_27891590[PMID]","terms":[{"hpo":"HP:0031831","label":"Decreased serum zinc","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001396","label":"Cholestasis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001395","label":"Hepatic fibrosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001397","label":"Hepatic steatosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002719","label":"Recurrent infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100511","label":"Abnormality of vitamin D metabolism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0410263","label":"Brain imaging abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010648","label":"Dermal translucency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000819","label":"Diabetes mellitus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006129","label":"Drumstick terminal phalanges","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000081","label":"Duplicated collecting system","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100633","label":"Esophagitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000293","label":"Full cheeks","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001399","label":"Hepatic failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001433","label":"Hepatosplenomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000126","label":"Hydronephrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000974","label":"Hyperextensible skin","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011342","label":"Mild global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001562","label":"Oligohydramnios","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000311","label":"Round face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001027","label":"Soft, doughy skin","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null}]}}