{"orpha":79318,"name":"PMM2-CDG","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CDG syndrome type Ia","CDG-Ia","CDG1A","Carbohydrate deficient glycoprotein syndrome type Ia","Congenital disorder of glycosylation type 1a","Congenital disorder of glycosylation type Ia","Phosphomannomutase 2 deficiency"],"definition":"A rare congenital disorder of N-glycosylation and is characterized by cerebellar dysfunction, abnormal fat distribution, inverted nipples, strabismus and hypotonia. 3 forms of PMM2-CDG can be distinguished: the infantile multisystem type, late-infantile and childhood ataxia-intellectual disability type (3-10 yrs old), and the adult stable disability type. Infants usually develop ataxia, psychomotor delay and extraneurological manifestations including failure to thrive, enteropathy, hepatic dysfunction, coagulation abnormalities and cardiac and renal involvement. The phenotype is however highly variable and ranges from infants who die in the first year of life to mildly involved adults.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-79318/","orphanet_url":"https://www.orpha.net/en/disease/detail/79318","names":{"fr":{"name":"PMM2-CDG","synonyms":["Anomalie congénitale de la glycosylation type 1a","Anomalie congénitale de la glycosylation type Ia","CDG1A","Déficit en phosphomannomutase 2","Syndrome CDG type Ia","Syndrome des glycoprotéines déficientes en hydrates de carbone type Ia"],"definition":"Forme la plus fréquente d'anomalie congénitale de la N-glycosylation caractérisée par un dysfonctionnement cérébelleux, une anomalie de répartition des graisses, des mamelons ombiliqués, un strabisme et une hypotonie. Il existe trois formes de PMM2-CDG : la forme multisystémique à début infantile, la forme à type de déficience intellectuelle-ataxie débutant à la fin de la petite enfance ou pendant l'enfance (de 3 à 10 ans) et la forme adulte à type d'atteinte stable. Les enfants en bas âge développent une ataxie, un retard psychomoteur et des manifestations extraneurologiques, dont un retard de croissance staturo-pondérale, une entéropathie, un dysfonctionnement hépatique, des anomalies de la coagulation et une atteinte cardiaque et rénale. Le phénotype est cependant très variable, certains enfants décédant au cours de la première année de vie alors que certains adultes ne présentent qu'une forme légère de la maladie."},"de":{"name":"PMM2-CDG","synonyms":["CDG1A","Kohlenhydrat-defizientes Glykoprotein-Syndrom Ia","Kongenitaler Defekt der Glycoproteinbiosynthese Typ Ia","Phosphomannomutase 2-Mangel","CDG-Ia","CDG-Syndrom Typ Ia"],"definition":"Eine seltene kongenitale Glykosylierungsstörung, die durch eine zerebelläre Dysfunktion, eine abnorme Fettverteilung, invertierte Brustwarzen, Strabismus und Hypotonie gekennzeichnet ist. Es lassen sich 3 Formen von PMM2-CDG unterscheiden: der infantile multisystemische Typ, der spätinfantile und kindliche Ataxie-intellektuelle Invaliditätstyp (3-10 Jahre alt) und der erwachsene stabile Invaliditätstyp. Säuglinge entwickeln in der Regel Ataxie, psychomotorische Entwicklungsverzögerung und extraneurologische Manifestationen, einschließlich Gedeihstörungen, Enteropathie, Leberfunktionsstörungen, Gerinnungsstörungen und Herz- und Nierenbeteiligung. Der Phänotyp ist jedoch sehr variabel und reicht von Säuglingen, die im ersten Lebensjahr sterben, bis hin zu leicht betroffenen Erwachsenen."},"es":{"name":"PMM2-CDG","synonyms":["CDG-Ia","CDG1A","Deficiencia de fosfomanomutasa 2","Síndrome CDG tipo Ia","Síndrome de glicoproteínas deficientes en carbohidratos tipo Ia","Trastorno congénito de la glicosilación tipo 1a","Trastorno congénito de la glicosilación tipo Ia"],"definition":"Es un trastorno congénito poco frecuente de la N-glicosilación y se caracteriza por disfunción cerebelosa, distribución anómala de la grasa, pezones invertidos, estrabismo e hipotonía. Se pueden distinguir 3 formas de PMM2-CDG: tipo multisistémico infantil, tipo ataxia-discapacidad intelectual de la lactancia tardía y la infancia (3-10 años), y tipo discapacidad estable del adulto. Por lo general, los lactantes desarrollan ataxia, retraso psicomotor y manifestaciones extraneurológicas que incluyen fallo de medro, enteropatía, disfunción hepática, anomalías de la coagulación y afectaciones cardíacas y renales. Sin embargo, el fenotipo es muy variable y va desde lactantes que fallecen en el primer año de vida hasta adultos levemente afectados."},"it":{"name":"PMM2-CDG","synonyms":["CDG-Ia","CDG1A","Deficit di fosfomannomutasi 2","Disturbo congenito della glicosilazione, tipo 1a","Disturbo congenito della glicosilazione, tipo Ia","Sindrome CDG, tipo Ia","Sindrome delle glicoproteine carenti in carboidrati, tipo Ia"],"definition":"La PMM2-CDG è la forma più comune di patologia congenita della N-glicosilazione. È caratterizzata da disfunzione cerebellare, anomala distribuzione del grasso, capezzoli introflessi, strabismo e ipotonia. Sono note tre forme di PMM2-CDG: una forma multisistemica neonatale, un forma ad esordio nella periodo neonatale tardivo e nell'adolescenza, con atassia e disabilità intellettiva (dai 3 ai 10 anni) e una forma adulta associata a disabilità stabile. Di solito i neonati presentano atassia, ritardo psicomotorio e sintomi extra-neurologici che comprendono ritardo della crescita, enteropatia, disfunzione epatica, anomalie della coagulazione e interessamento cardiaco e renale. Il quadro clinico è molto variabile; alcuni pazienti muoiono nel primo anno di vita, mentre alcuni adulti presentano solo una forma lieve della malattia."},"nl":{"name":"PMM2-CDG","synonyms":["Congenitale defecten van de glycosylering type Ia","Congenitale glycosylatiestoornis type Ia","Fosfomannomutase 2-deficiëntie","Koolhydraatdeficiënt glycoproteïne-syndroom type Ia","CDG-Ia","CDG-syndroom type Ia","CDG1A","Congenitale glycosylatiestoornis type 1a","Congenitale defecten van de glycosylering type 1a"],"definition":"Een zeldzame congenitale stoornis van N-glycosylatie, gekenmerkt door cerebellaire disfunctie, abnormale verdeling van vet, geïnverteerde tepels, strabisme en hypotonie. Er kunnen drie vormen van PMM2-CDG onderscheiden worden: het infantiele multisystemische type, het laat-infantiele en in de kindertijd optredende type met ataxie-intellectuele achterstand (3-10 jaar oud), en het volwassen stabiele type met invaliditeit. Zuigelingen ontwikkelen meestal ataxie, psychomotorische achterstand en extraneurologische manifestaties waaronder niet-gedijen, enteropathie, leverdisfunctie, coagulatiestoornissen, en betrokkenheid van hart en nieren. Het fenotype is echter zeer variabel en gaat van zuigelingen die overlijden in hun eerste levensjaar tot volwassenen die slechts licht aangetast zijn."},"pt":{"name":"PMM2-CDG","synonyms":["CDG-Ia","CDG1A","Deficiência de fosfomanomutase 2","Doença congénita da glicosilação tipo 1a","Doença congénita da glicosilação tipo Ia","Síndrome CDG tipo Ia","Síndrome de glicoproteína deficiente em carbohidratos tipo Ia"]},"pl":{"name":"PMM2-CDG","synonyms":["CDG1A","CDG-Ia","Niedobór fosfomannomutazy 2","Wrodzone zaburzenie glikozylacji typu 1a","Wrodzone zaburzenie glikozylacji typu Ia","Zespół CDG typu Ia","Zespół obniżonej glikozylacji glikoprotein typu Ia"],"definition":"Rzadkie wrodzone zaburzenie N-glikozylacji, charakteryzujące się dysfunkcją móżdżku, nieprawidłowym rozmieszczeniem tkanki tłuszczowej, wklęsłymi sutkami, zezem i hipotonią. Można wyróżnić 3 formy PMM2-CDG: dziecięcy typ wielosystemowy, późnoniemowlęcy i dziecięcy typ ataksji-niepełnosprawności intelektualnej (3-10 lat) oraz typ stabilnej niepełnosprawności dorosłej. U niemowląt zwykle rozwija się ataksja, opóźnienie psychoruchowe i objawy pozaneurologiczne, w tym brak prawidłowego rozwoju, enteropatia, zaburzenia czynności wątroby, zaburzenia krzepnięcia oraz zajęcie serca i nerek. Fenotyp jest jednak bardzo zmienny: od chorych, którzy umierają w pierwszym roku życia, po osoby dorosłe z łagodnym przebiegiem choroby."},"cs":{"name":"PMM2-CDG","synonyms":["CDG syndrom, typ Ia","CDG-Ia","CDG1A","Carbohydrate deficient glycoprotein syndrom type Ia","Vrozená porucha glykosylace, typ 1a","Vrozená porucha glykosylace, typ Ia","Deficit fosfomannomutázy 2","Syndrom s deficitem karbohydrátového glykoproteinu typ Ia"]},"uk":{"name":"PMM2-CDG","synonyms":["Вуглеводно-дефіцитний глікопротеїновий синдром типу Ia","Синдром CDG, тип Ia","CDG1A","CDG-Іа","Вроджене порушення глікозилювання типу 1а","Вроджене порушення глікозилювання типу Ia","Дефіцит фосфоманномутази 2"],"definition":"A rare congenital disorder of N-glycosylation and is characterized by cerebellar dysfunction, abnormal fat distribution, inverted nipples, strabismus and hypotonia. 3 forms of PMM2-CDG can be distinguished: the infantile multisystem type, late-infantile and childhood ataxia-intellectual disability type (3-10 yrs old), and the adult stable disability type. Infants usually develop ataxia, psychomotor delay and extraneurological manifestations including failure to thrive, enteropathy, hepatic dysfunction, coagulation abnormalities and cardiac and renal involvement. The phenotype is however highly variable and ranges from infants who die in the first year of life to mildly involved adults."},"zh":{"name":"先天性糖基化障碍1a型","synonyms":["碳水化合物缺乏糖蛋白综合征Ia型"]},"tr":{"name":"PMM2-CDG","synonyms":["CDG1A","CDG-Ia","CDG sendromu tip Ia","Fosfomannomutaz 2 eksikliği","Tip 1a'nın doğumsal glikozilasyon bozukluğu","Tip Ia'nın Doğumsal bozukluğu","Karbonhidrat eksikliği olan glikoprotein sendromu tip Ia"]}},"xrefs":[{"source":"OMIM","code":"212065","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":"491821390"},{"source":"MONDO","code":"0008907","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C535739","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0349653","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"9826","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":371071,"name":"Congenital disorder of glycosylation with epilepsy as a major feature","classifications":[156,181]},{"orpha":371157,"name":"Congenital disorder of glycosylation with hepatic involvement","classifications":[156,183]},{"orpha":371200,"name":"Congenital disorder of glycosylation with skin involvement","classifications":[156,187]},{"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":"PMM2","name":"phosphomannomutase 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301289[PMID]_20301507[PMID]","hgnc":"9115","ensembl":"ENSG00000140650","omim":"601785","loci":["16p13.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":1.73,"area":"Italy","status":"Validated","source":"11953730[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_19862844[PMID]"},{"type":"Prevalence at birth","qualification":"Class only","class":"1-9 / 100 000","value":0.0,"area":"Europe","status":"Validated","source":"10854097[PMID]_11953730[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-04-11","source":"29079546[PMID]_29229467[PMID]_28425223[PMID]_30464053[PMID]_20301289[PMID]","terms":[{"hpo":"HP:0000218","label":"High palate","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007552","label":"Abnormal subcutaneous fat tissue distribution","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003186","label":"Inverted nipples","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002751","label":"Kyphoscoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009125","label":"Lipodystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000276","label":"Long face","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100807","label":"Long fingers","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000303","label":"Mandibular prognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000939","label":"Osteoporosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011220","label":"Prominent forehead","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000448","label":"Prominent nose","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000278","label":"Retrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000154","label":"Wide mouth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030146","label":"Abnormal liver parenchyma morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000377","label":"Abnormal pinna morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000091","label":"Abnormal renal tubule morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011443","label":"Abnormality of coordination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011842","label":"Abnormality of skeletal morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010463","label":"Aplasia of the ovary","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011951","label":"Aspiration pneumonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008734","label":"Decreased testicular size","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000845","label":"Elevated circulating growth hormone concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002925","label":"Elevated circulating thyroid-stimulating hormone concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002280","label":"Enlarged cisterna magna","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001945","label":"Fever","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001395","label":"Hepatic fibrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000842","label":"Hyperinsulinemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012882","label":"Hyperplastic labia majora","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003073","label":"Hypoalbuminemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000044","label":"Hypogonadotropic hypogonadism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000870","label":"Increased circulating prolactin concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000855","label":"Insulin resistance","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002828","label":"Multiple joint contractures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005562","label":"Multiple renal cysts","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000100","label":"Nephrotic syndrome","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001698","label":"Pericardial effusion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009830","label":"Peripheral neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030609","label":"Photoreceptor layer loss on macular OCT","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000426","label":"Prominent nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000093","label":"Proteinuria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001976","label":"Reduced antithrombin III activity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011858","label":"Reduced factor IX activity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001929","label":"Reduced factor XI activity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012509","label":"Reduced thyroxin-binding globulin","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002098","label":"Respiratory distress","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000510","label":"Rod-cone dystrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012050","label":"Anasarca","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001681","label":"Angina pectoris","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001305","label":"Dandy-Walker malformation","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002625","label":"Deep venous thrombosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0031404","label":"Impaired antigen-specific response","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0040238","label":"Impaired neutrophil chemotaxis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002170","label":"Intracranial hemorrhage","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001004","label":"Lymphedema","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001701","label":"Pericarditis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000926","label":"Platyspondyly","frequency":"Very rare (<4-1%)","criteria":null}]}}