{"orpha":79324,"name":"ALG12-CDG","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Congenital disorder of glycosylation type Ig","Mannosyltransferase 8 deficiency","CDG syndrome type Ig","CDG-Ig","CDG1G","Carbohydrate deficient glycoprotein syndrome type Ig","Congenital disorder of glycosylation type 1g"],"definition":"A form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (prominent forehead, large ears, thin upper lip), generalized hypotonia, feeding difficulties, moderate to severe developmental delay, progressive microcephaly, frequent upper respiratory tract infections due to impaired immunity with decreased immunoglobulin levels, and decreased coagulation factors. Additional features include hypogonadism with or without hypospadias in males, skeletal anomalies, seizures and cardiac anomalies in some cases. The disease is caused by loss of function mutations of the gene <i>ALG12</i> (22q13.33).","note":null,"url":"https://raremap.alftech.space/d/ORPHA-79324/","orphanet_url":"https://www.orpha.net/en/disease/detail/79324","names":{"fr":{"name":"ALG12-CDG","synonyms":["Anomalie congénitale de la glycosylation type 1g","Anomalie congénitale de la glycosylation type Ig","CDG-Ig","CDG1G","Déficit en mannosyltransférase 8","Syndrome CDG type Ig","Syndrome des glycoprotéines déficientes en hydrates de carbone Ig"],"definition":"Forme d'anomalie congénitale de la N-glycosylation caractérisée par une dysmorphie faciale (front proéminent, grandes oreilles, lèvre supérieure fine), une hypotonie généralisée, des difficultés à s'alimenter, un retard de développement modéré à sévère, une microcéphalie progressive, des infections fréquentes des voies respiratoires supérieures dues à un déficit immunitaire, une diminution des taux d'immunoglobulines, et une diminution des facteurs de coagulation. Les autres caractéristiques sont un hypogonadisme avec ou sans hypospadias chez les hommes, des anomalies squelettiques, des crises d'épilepsie et des anomalies cardiaques dans certains cas. La maladie est causée par des mutations de perte de fonction du gène&nbsp;<i>ALG12</i> (22q13.33)."},"de":{"name":"ALG12-CDG","synonyms":["CDG-Ig","CDG-Syndrom Typ Ig","CDG1G","Kohlenhydrat-defizientes Glykoprotein-Syndrom Ig","Kongenitaler Defekt der Glycoproteinbiosynthese Typ Ig","Mannosyltransferase 8-Mangel"],"definition":"Die Kongenitalen Glykosylierungs-Defekt (CDG)-Syndrome sind eine Gruppe angeborener Stoffwechselstörungen mit gestörter Synthese von Glykoproteinen. Das CDG-Syndrom Typ Ig (CDG 1G) ist gekennzeichnet durch Gesichtsdysmorphien (hohe Stirn, große Ohren, dünne Oberlippe), generalisierte Hypotonie, Schwierigkeiten bei der Nahrungsaufnahme, mäßige bis schwere Entwicklungsverzögerung, fortschreitende Mikrozephalie, häufige Infektionen der oberen Atemwege aufgrund einer beeinträchtigten Immunität mit verminderten Immunglobulinwerten und verminderten Gerinnungsfaktoren gekennzeichnet ist. Weitere Merkmale sind Hypogonadismus mit oder ohne Hypospadie bei Männern, Skelettanomalien, Krampfanfälle und in einigen Fällen Herzanomalien. Ursache des CDG 1G sind inaktivierende Mutationen im <i>ALG12</i>-Gen, das auf dem Chromosom 22 liegt und die Alpha-1,6-Mannosyltransferase des endoplasmatischen Retikulums kodiert."},"es":{"name":"ALG12-CDG","synonyms":["CDG-Ig","CDG1G","Deficiencia de manosiltransferasa 8","Síndrome CDG tipo Ig","Síndrome de glicoproteínas deficientes en carbohidratos tipo Ig","Trastorno congénito de la glicosilación tipo 1g","Trastorno congénito de la glicosilación tipo Ig"],"definition":"Es un trastorno congénito de la N-glicosilación caracterizado por dismorfia facial (frente prominente, orejas de gran tamaño, labio superior delgado), hipotonía generalizada, problemas en la alimentación, retraso en el desarrollo de moderado a grave, microcefalia progresiva, infecciones frecuentes del tracto respiratorio superior debidas a alteraciones del sistema inmunitario con disminución de los niveles de inmunoglobulina y de los factores de coagulación. Otros hallazgos adicionales incluyen hipogonadismo con o sin hipospadias en varones, anomalías esqueléticas, convulsiones y, en algunos casos, anomalías cardíacas. La enfermedad está causada por mutaciones de pérdida de función del gen <i>ALG12</i> (22q13.33)."},"it":{"name":"ALG12-CDG","synonyms":["CDG-Ig","CDG1G","Deficit di mannosiltransferasi 8","Disturbo congenito della glicosilazione, tipo 1g","Disturbo congenito della glicosilazione, tipo Ig","Sindrome CDG, tipo Ig","Sindrome delle glicoproteine carenti in carboidrati, tipo Ig"],"definition":"L'ALG12-CDG è una malattia congenita della N-glicosilazione, caratterizzata da dismorfismi facciali (fronte prominente, orecchie grandi, labbro superiore sottile), ipotonia generalizzata, difficoltà di alimentazione, ritardo dello sviluppo moderato o grave, microcefalia progressiva, frequenti infezioni delle vie aeree superiori secondarie alla compromissione immunitaria, riduzione dei livelli delle immunoglobuline e dei fattori della coagulazione. Altri segni clinici sono l'ipogonadismo con o senza ipospadia nei maschi, le anomalie scheletriche, le crisi epilettiche e, in alcuni pazienti, le cardiopatie. L'ALG12-CDG è causata da alcune mutazioni con perdita di funzione nel gene <i>ALG12</i> (22q13.33)."},"nl":{"name":"ALG12-CDG","synonyms":["CDG-Ig","CDG-syndroom type Ig","CDG1G","Congenitale defecten van de glycosylering type 1g","Congenitale defecten van de glycosylering type Ig","Congenitale glycosylatiestoornis type 1g","Congenitale glycosylatiestoornis type Ig","Koolhydraatdeficiënt glycoproteïne-syndroom Ig","Mannosyltransferase 8-deficiëntie"],"definition":"Een vorm van congenitale stoornis van N-glycosylatie, gekarakteriseerd door faciale dysmorfie (uitgesproken voorhoofd, grote oren, dunne bovenlip), gegeneraliseerde hypotonie, voedingsproblemen, matige tot ernstige ontwikkelingsachterstand, progressieve microcefalie, frequente infecties van de bovenste luchtwegen door verstoorde immuniteit met verlaagde immunoglobulinegehaltes, en verminderde hoeveelheid coagulatiefactoren. Bijkomende kenmerken zijn onder meer hypogonadisme met of zonder hypospadieën bij mannen, skeletanomalieën, insulten en hartanomalieën in sommige gevallen. De ziekte wordt veroorzaakt door mutaties met functieverlies in het gen <i>ALG12</i> (22q13.33)."},"pt":{"name":"ALG12-CDG","synonyms":["Doença congénita da glicosilação tipo Ig","Síndrome CDG tipo Ig","Síndrome de glicoproteína deficiente em carbohidratos tipo Ig","CDG-Ig","CDG1G","Deficiência de manosiltransferase 8","Doença congénita da glicosilação tipo 1g"]},"pl":{"name":"ALG12-CDG","synonyms":["CDG1G","CDG-Ig","Niedobór mannozylotransferazy 8","Wrodzone zaburzenie glikozylacji typu Ig","Wrodzone zaburzenie glikozylacji typu Ig","Zespół CDG typu Ig","Zespół obniżonej glikozylacji glikoprotein typu Ig"]},"cs":{"name":"ALG12-CDG","synonyms":["CDG syndrom, typ Ig","CDG-Ig","CDG1G","Carbohydrate deficient glycoprotein syndrom type Ig","Vrozená porucha glykosylace, typ 1g","Vrozená porucha glykosylace, typ Ig","Deficit mannosyltransferázy 8","Syndrom s deficitem karbohydrátového glykoproteinu typ Ig"]},"uk":{"name":"ALG12-CDG","synonyms":["Вуглеводно-дефіцитний глікопротеїновий синдром типу Ig","Синдром CDG, тип Ig","CDG1G","CDG-Ig","Вроджене порушення глікозилювання типу 1g","Вроджене порушення глікозилювання типу Ig","Дефіцит маннозилтрансферази 8"],"definition":"A form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (prominent forehead, large ears, thin upper lip), generalized hypotonia, feeding difficulties, moderate to severe developmental delay, progressive microcephaly, frequent upper respiratory tract infections due to impaired immunity with decreased immunoglobulin levels, and decreased coagulation factors. Additional features include hypogonadism with or without hypospadias in males, skeletal anomalies, seizures and cardiac anomalies in some cases. The disease is caused by loss of function mutations of the gene <i>ALG12</i> (22q13.33)."},"zh":{"name":"先天性糖基化障碍1g型","synonyms":["碳水化合物缺乏糖蛋白综合征Ig型"]},"tr":{"name":"ALG12-CDG","synonyms":["CDG1G","CDG-Ig","CDG sendromu tip Ig","Mannosiltransferaz 8 eksikliği","Glikozilasyon tip 1g'nin Doğumsal bozukluğu","Glikozilasyon tip Ig'nin Doğumsal bozukluğu","Karbonhidrat eksikliği olan glikoprotein sendromu tip Ig"]}},"xrefs":[{"source":"OMIM","code":"607143","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E77.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C54.0","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"160861812"},{"source":"MONDO","code":"0011783","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C535745","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2931001","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"9833","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":371047,"name":"Congenital disorder of glycosylation with neurological involvement","classifications":[156,181]},{"orpha":309347,"name":"Disorder of protein N-glycosylation","classifications":[150,156]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"ALG12","name":"ALG12 alpha-1,6-mannosyltransferase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301507[PMID]","hgnc":"19358","ensembl":"ENSG00000182858","omim":"607144","loci":["22q13.33"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":11.0,"area":"Worldwide","status":"Validated","source":"22516080[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_22516080[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-09-13","source":"20301507[PMID]_31481313[PMID]","terms":[{"hpo":"HP:0012379","label":"Abnormal enzyme/coenzyme activity","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0003256","label":"Abnormality of the coagulation cascade","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000119","label":"Abnormality of the genitourinary system","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0410242","label":"Abnormal IgG level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000759","label":"Abnormal peripheral nervous system morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002257","label":"Chronic rhinitis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010976","label":"Decreased total B cell count","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002194","label":"Delayed gross motor development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002011","label":"Morphological central nervous system abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000253","label":"Progressive microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003645","label":"Prolonged partial thromboplastin time","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008151","label":"Prolonged prothrombin time","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0410018","label":"Recurrent ear infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100776","label":"Recurrent pharyngitis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006532","label":"Recurrent pneumonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002205","label":"Recurrent respiratory infections","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040246","label":"Reduced antithrombin antigen","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001929","label":"Reduced factor XI activity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005543","label":"Reduced protein C activity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004855","label":"Reduced protein S activity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0410240","label":"Abnormal IgA level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0410243","label":"Abnormal IgM level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011849","label":"Abnormal bone ossification","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000377","label":"Abnormal pinna morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000478","label":"Abnormality of the eye","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0410263","label":"Brain imaging abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012385","label":"Camptodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002389","label":"Cavum septum pellucidum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004209","label":"Clinodactyly of the 5th finger","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0410295","label":"Complete or near-complete absence of specific antibody response to tetanus vaccine","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030353","label":"Decreased serum insulin-like growth factor 1","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011471","label":"Gastrostomy tube feeding in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003073","label":"Hypoalbuminemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003146","label":"Hypocholesterolemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000276","label":"Long face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100807","label":"Long fingers","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002162","label":"Low posterior hairline","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000054","label":"Micropenis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011800","label":"Midface retrusion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010557","label":"Overlapping fingers","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001302","label":"Pachygyria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0410305","label":"Partial absence of specific antibody response to Haemophilus influenzae type b (Hib) vaccine","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011327","label":"Posterior plagiocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001622","label":"Premature birth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000426","label":"Prominent nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009623","label":"Proximal placement of thumb","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001988","label":"Recurrent hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001582","label":"Redundant skin","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000541","label":"Retinal detachment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001852","label":"Sandal gap","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","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:0011344","label":"Severe global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003026","label":"Short long bone","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000322","label":"Short philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001792","label":"Small nail","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001762","label":"Talipes equinovarus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001873","label":"Thrombocytopenia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003049","label":"Ulnar deviation of the wrist","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000445","label":"Wide nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012766","label":"Widened cerebral subarachnoid space","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009124","label":"Abnormal adipose tissue morphology","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0200128","label":"Biventricular hypertrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000969","label":"Edema","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002902","label":"Hyponatremia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002566","label":"Intestinal malrotation","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003186","label":"Inverted nipples","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0011623","label":"Muscular ventricular septal defect","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001655","label":"Patent foramen ovale","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0100806","label":"Sepsis","frequency":"Very rare (<4-1%)","criteria":null}]}}