{"orpha":468699,"name":"SLC39A8-CDG","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CDG syndrome type IIn","CDG-IIn","CDG2N","Carbohydrate deficient glycoprotein syndrome type IIn","Congenital disorder of glycosylation type 2n","Congenital disorder of glycosylation type IIn","SLC39A8 deficiency"],"definition":"A rare congenital disorder of glycosylation characterized by infantile onset of global developmental delay, severe intellectual disability, hypotonia, and variable additional features including short stature, cranial asymmetry, seizures, strabismus, recurrent infections, and osteopenia, among others. Laboratory analysis reveals decreased blood levels of zinc and manganese, as well as an abnormal serum transferrin glycosylation pattern with decreased tetrasialo- and increased asialo-, monosialo-, disialo, and trisialo-transferrin, consistent with a type II congenital disorder of glycosylation. Brain imaging shows cerebellar and/or cerebral atrophy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-468699/","orphanet_url":"https://www.orpha.net/en/disease/detail/468699","names":{"fr":{"name":"SLC39A8-CDG","synonyms":["Anomalie congénitale de la glycosylation type 2n","Anomalie congénitale de la glycosylation type IIn","CDG-IIn","CDG2N","Syndrome CDG type IIn","Syndrome des glycoprotéines déficientes en hydrates de carbone type IIn"],"definition":"Anomalie congénitale rare de la glycosylation caractérisée par l'apparition infantile d'un retard global du développement, d'une déficience intellectuelle sévère, d'une hypotonie et d'autres signes cliniques variables, à savoir, une petite taille, une asymétrie crânienne, des crises convulsives, un strabisme, des infections récurrentes et une ostéopénie. Les examens biologiques révèlent une diminution des taux sanguins de zinc et de manganèse, ainsi qu'un profil anormal de glycosylation de la transferrine sérique avec une diminution de la tétrasialotransferrine et une augmentation de l'asialotransferrine, du monosialotransferrine, du disialotransferrine et de la trisialo-transferrine, évocatrices d'une anomalie congénitale de la glycosylation de type II. L'IRM révèle une atrophie cérébelleuse et/ou cérébrale."},"de":{"name":"SLC39A8-CDG","synonyms":["CDG (Congenital Disorder of Glycosylation) Typ IIn","CDG-IIn","CDG-Syndrom Typ 2n","CDG-Syndrom Typ IIn","CDG2n","Kohlenhydrat-defizientes Glykoprotein-Syndrom 2n","Kongenitaler Defekt der Glycoproteinbiosynthese Typ IIn","SLC39A8-Mangel"],"definition":"Eine seltene kongenitale Glykosylierungsstörung, die sich durch eine im Säuglingsalter einsetzende globale Entwicklungsverzögerung, schwere Intelligenzminderung, Hypotonie und variable zusätzliche Merkmale wie Kleinwuchs, Schädelasymmetrie, Krampfanfälle, Strabismus, wiederkehrende Infektionen und Osteopenie auszeichnet. Die Laboranalyse zeigt verringerte Zink- und Manganwerte im Blut sowie ein abnormales Serum-Transferrin-Glykosylierungsmuster mit verringertem Tetrasialo- und erhöhtem Asialo-, Monosialo-, Disialo- und Trisialo-Transferrin, was einer Kongenitalen Glykosylierungsstörung vom Typ II entspricht. Die Bildgebung des Gehirns zeigt eine Atrophie des Kleinhirns und/oder des Großhirns."},"es":{"name":"SLC39A8-CDG","synonyms":["CDG-IIn","CDG2N","Deficiencia de SLC39A8","Síndrome CDG tipo IIn","Síndrome de glicoproteínas deficientes en carbohidratos tipo IIn","Trastorno congénito de la glicosilación tipo 2n","Trastorno congénito de la glicosilación tipo IIn"],"definition":"Es un trastorno congénito y poco frecuente de la glicosilación caracterizado por un inicio en la lactancia de retraso global del desarrollo, grave discapacidad intelectual, hipotonía y otros hallazgos adicionales variables, incluyendo talla baja, asimetría craneal, crisis epilépticas, estrabismo, infecciones recurrentes y osteopenia, entre otros. Las pruebas analíticas revelan niveles reducidos de zinc y manganeso en sangre, así como un patrón de glicosilación anómalo de la transferrina sérica con disminución de la tetrasialo-transferrina y aumento de la asialo-, monosialo-, disialo- y trisialo-transferrina, consistente con un trastorno congénito de la glicosilación tipo II. La neuroimagen muestra atrofia cerebelosa y/o cerebral."},"it":{"name":"SLC39A8-CDG","definition":"Si tratta di una malattia congenita rara della glicosilazione, caratterizzata da ritardo dello sviluppo globale ad esordio infantile, disabilità intellettiva grave, ipotonia e altri segni clinici variabili che comprendono la bassa statura, l'asimmetria cranica, le crisi epilettiche, lo strabismo, le infezioni ricorrenti e l'osteopenia. Le analisi di laboratorio evidenziano livelli ridotti di zinco e manganese nel sangue, anomalie della glicosilazione della transferrina nel siero con riduzione della tetrasialo-transferrina e aumento della asialo-, monosialo-, disialo- e trisialo-transferrina, coerente con una malattia congenita della glicosilazione di tipo II. Le neuroimmagini evidenziano atrofia cerebellare e/o cerebrale."},"nl":{"name":"SLC39A8-CDG","synonyms":["CDG-IIn","CDG-syndroom type 2n","CDG-syndroom type IIn","CDG2N","Congenitale defecten van de glycosylering type 2n","Congenitale defecten van de glycosylering type IIn","Congenitale glycosylatiestoornis type 2n","Congenitale glycosylatiestoornis type IIn","SLC39A8-deficiëntie"],"definition":"Een zeldzame congenitale glycosylatiestoornis, gekarakteriseerd door infantiele aanvang van algehele ontwikkelingsachterstand, ernstige intellectuele achterstand, hypotonie, en variabele bijkomende kenmerken waaronder kleine gestalte, asymmetrie van schedel, insulten, strabisme, recidiverende infecties, en osteopenie. Laboratoriumanalyse toont verlaagde gehaltes van zink en mangaan in bloed, alsook abnormaal glycosylatiepatroon van transferrine in serum met verminderd tetrasialo- en verhoogd asialo-, monosialo-, disialo-, en trisialo-transferrine, consistent met een congenitale glycosylatiestoornis type II. Beeldvorming van hersenen toont cerebellaire en/of cerebrale atrofie."},"pt":{"name":"SLC39A8-CDG","synonyms":["CDG-IIn","CDG2N","Deficiência SLC39A8","Doença congénita da glicosilação tipo 2n","Doença congénita da glicosilação tipo IIn","Síndrome CDG tipo IIn","Síndrome de glicoproteína deficiente em carbohidratos tipo IIn"]},"pl":{"name":"SLC39A8-CDG","synonyms":["CDG2N","CDG-IIn","Niedobór SLC39A8","Zespół CDG typu IIn","Wrodzone zaburzenie glikozylacji typu 2n","Wrodzone zaburzenie glikozylacji typu IIn","Zespół obniżonej glikozylacji glikoprotein typ IIn"]},"cs":{"name":"SLC39A8-CDG","synonyms":["CDG2N","CDG-IIn","SLC39A8 deficiency","CDG syndrome type IIn","Congenital disorder of glycosylation type 2n","Congenital disorder of glycosylation type IIn","Carbohydrate deficient glycoprotein syndrome type IIn","SLC39A8 deficit","CDG syndrom typ IIn","Vrozená porucha glykosylace typ 2n","Vrozená porucha glykosylace typ IIn","Glykoproteinový syndrom deficitu sacharidů typu IIn"]},"uk":{"name":"SLC39A8-CDG","synonyms":["Вуглеводно-дефіцитний глікопротеїновий синдром типу IIn","Синдром CDG, тип IIn","CDG2N","CDG-IIn","Вроджене порушення глікозилювання типу 2n","Вроджене порушення глікозилювання типу IIn","Дефіцит SLC39A8"],"definition":"A rare congenital disorder of glycosylation characterized by infantile onset of global developmental delay, severe intellectual disability, hypotonia, and variable additional features including short stature, cranial asymmetry, seizures, strabismus, recurrent infections, and osteopenia, among others. Laboratory analysis reveals decreased blood levels of zinc and manganese, as well as an abnormal serum transferrin glycosylation pattern with decreased tetrasialo- and increased asialo-, monosialo-, disialo, and trisialo-transferrin, consistent with a type II congenital disorder of glycosylation. Brain imaging shows cerebellar and/or cerebral atrophy."},"zh":{"name":"SLC39A8相关糖基化障碍疾病","synonyms":["碳水化合物缺乏糖蛋白综合征lln型"]},"tr":{"name":"SLC39A8-CDG","synonyms":["CDG2N","CDG-IIn","SLC39A8 eksikliği","CDG sendromu tip IIn","Tip 2n'nin doğumsal bozukluğu","Tip IIn glikozilasyonunun doğumsal bozukluğu","Karbonhidrat eksikliği glikoprotein sendromu tip IIn"]}},"xrefs":[{"source":"OMIM","code":"616721","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":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0014746","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4225234","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":309851,"name":"Disorder of manganese transport","classifications":[150,156]},{"orpha":309347,"name":"Disorder of protein N-glycosylation","classifications":[150,156]},{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":269567,"name":"Genetic syndrome with a cerebellar malformation as a major feature","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":269523,"name":"Syndrome with a cerebellar malformation as a major feature","classifications":[147,181]}],"children":[],"genes":[{"symbol":"SLC39A8","name":"solute carrier family 39 member 8","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26637978[PMID]_26637979[PMID]","hgnc":"20862","ensembl":"ENSG00000138821","omim":"608732","loci":["4q24"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":10.0,"area":"Worldwide","status":"Validated","source":"26637978[PMID]_26637979[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26637978[PMID]_26637979[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-09-26","source":"27995398[PMID]_26637979[PMID]_26637978[PMID]","terms":[{"hpo":"HP:0008277","label":"Abnormality of zinc homeostasis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0032098","label":"Hypomanganesemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002187","label":"Intellectual disability, profound","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012736","label":"Profound global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0006829","label":"Severe muscular hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012301","label":"Type II transferrin isoform profile","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001531","label":"Failure to thrive in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025405","label":"Visual fixation instability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001392","label":"Abnormality of the liver","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000483","label":"Astigmatism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001363","label":"Craniosynostosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010621","label":"Cutaneous syndactyly of toes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008314","label":"Decreased activity of mitochondrial complex II","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008347","label":"Decreased activity of mitochondrial complex IV","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002928","label":"Decreased activity of the pyruvate dehydrogenase complex","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006558","label":"Decreased mitochondrial complex III activity in liver tissue","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008873","label":"Disproportionate short-limb short stature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002987","label":"Elbow flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012368","label":"Flat face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000540","label":"Hypermetropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002521","label":"Hypsarrhythmia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002490","label":"Increased CSF lactate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006380","label":"Knee flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009826","label":"Limb undergrowth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002719","label":"Recurrent infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002882","label":"Sudden episodic apnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null}]}}