{"orpha":98434,"name":"Hereditary combined deficiency of vitamin K-dependent clotting factors","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Hereditary combined deficiency of factors II, VII, IX and X"],"definition":"Combined vitamin K-dependent clotting factors deficiency (VKCFD) is a congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X, as well as natural anticoagulants protein C, protein S and protein Z.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-98434/","orphanet_url":"https://www.orpha.net/en/disease/detail/98434","names":{"fr":{"name":"Déficit héréditaire combiné en facteurs de la coagulation dépendants de la vitamine K","synonyms":["Déficit héréditaire combiné en facteur II, VII, IX et X"],"definition":"Le déficit combiné en facteurs vitamine K-dépendants (VKD) est une maladie hémorragique congénitale due à la diminution variable du taux des facteurs de coagulation II, VII , IX et X et des protéines anticoagulantes naturelles C, S et Z."},"de":{"name":"Vitamin K-abhängige Gerinnungsfaktoren, hereditärer kombinierter Mangel","synonyms":["Faktoren II, VII, IX und X, hereditärer kombinierter Mangel"],"definition":"Der Hereditäre kombinierte Mangel der Vitamin K-abhängigen Gerinnungsfaktoren (VKCFD) ist eine kongenitale Blutungsneigung als Folge einer unterschiedlich starken Verminderung der Gerinnungsfaktoren II, VII, IX und X, sowie der Vitamin K-abhängig in der Leber synthetisierten, blutgerinnungshemmenden Proteine C, S und Z."},"es":{"name":"Deficiencia combinada de factores de la coagulación dependientes de la vitamina K, forma hereditaria","synonyms":["Deficiencia combinada hereditaria de factores II, VII, IX y X"],"definition":"El déficit combinado de factores de la coagulación vitamina K dependientes hereditario (VKCFD) es un trastorno hemorrágico congénito, consecuencia de una disminución de los niveles de los factores de coagulación II, VII, IX y X, así como de anticoagulantes naturales como son las proteínas C, S y Z."},"it":{"name":"Deficit combinato ereditario dei fattori della coagulazione dipedenti dalla vitamina K","synonyms":["Deficit combinato ereditario dei fattori II, VII, IX e X"]},"nl":{"name":"Hereditaire gecombineerde deficiëntie van vitamine K-afhankelijke stollingsfactoren","synonyms":["Erfelijke gecombineerde deficiëntie van factoren II, VII, IX en X"],"definition":"Een congenitale stollingsstoornis, als gevolg van variabel verminderde gehaltes van stollingsfactoren II, VII, IX en X, alsook van natuurlijke anticoagulantia proteïne C, proteïne S en proteïne Z."},"pt":{"name":"Deficiência combinada hereditária dos fatores de coagulação vitamina K-dependente"},"pl":{"name":"Dziedziczny złożony niedobór czynników krzepnięcia zależnych od witaminy K","synonyms":["Hereditary combined deficiency of factors II, VII, IX and X"]},"cs":{"name":"Dědičný kombinovaný deficit vitamin K-dependentních koagulačních faktorů","synonyms":["Dědičný kombinovaný deficit faktorů II, VII, IX a X"]},"uk":{"name":"Спадковий комбінований дефіцит вітамін К-залежних факторів згортання крові","synonyms":["Спадковий комбінований дефіцит факторів II, VII, IX і X"],"definition":"Combined vitamin K-dependent clotting factors deficiency (VKCFD) is a congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X, as well as natural anticoagulants protein C, protein S and protein Z."},"zh":{"name":"遗传性维生素K依赖性凝血因子复合缺乏症","synonyms":["遗传性II/VII/IX/X因子复合缺乏症"],"definition":"联合维生素K依赖凝血因子缺乏症(VKCFD)是一种先天性出血性疾病，由凝血因子II、VII、IX和X以及天然抗凝剂蛋白C、蛋白S和蛋白Z水平不同程度降低引起。"},"tr":{"name":"K vitaminine bağlı pıhtılaşma faktörlerinin kalıtsal kombine eksikliği","synonyms":["II, VII, IX ve X faktörlerinin kalıtsal kombine eksikliği"]}},"xrefs":[{"source":"OMIM","code":"277450","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"607473","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"D68.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"3B14.2","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"54644599"},{"source":"MONDO","code":"0015722","qualifier":"E","icd_relation":null,"validated":true},{"source":"MONDO","code":"15722","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4510617","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":97992,"name":"Rare hematologic disease"},"parents":[{"orpha":169826,"name":"Congenital vitamin K-dependent coagulation factors deficiency","classifications":[156,194]},{"orpha":309833,"name":"Disorder of other vitamins and cofactors metabolism and transport","classifications":[150,156]}],"children":[],"genes":[{"symbol":"GGCX","name":"gamma-glutamyl carboxylase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"16720838[PMID]","hgnc":"4247","ensembl":"ENSG00000115486","omim":"137167","loci":["2p11.2"]},{"symbol":"VKORC1","name":"vitamin K epoxide reductase complex subunit 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"14765194[PMID]","hgnc":"23663","ensembl":"ENSG00000167397","omim":"608547","loci":["16p11.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Adolescent","Adult","Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":272.0,"area":"Worldwide","status":"Validated","source":"39496305[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_20630065[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2025-12-01","source":"40541254[PMID]_39496305[PMID]_20630065[PMID]","terms":[{"hpo":"HP:0001892","label":"Abnormal bleeding","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000978","label":"Bruising susceptibility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040226","label":"Decreased level of heparin co-factor II","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:0011858","label":"Reduced factor IX activity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008169","label":"Reduced factor VII activity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008321","label":"Reduced factor X 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:0001102","label":"Angioid streaks of the fundus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002621","label":"Atherosclerosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012541","label":"Cephalohematoma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000973","label":"Cutis laxa","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031364","label":"Ecchymosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010655","label":"Epiphyseal stippling","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000421","label":"Epistaxis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004646","label":"Hypoplasia of the nasal bone","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002170","label":"Intracranial hemorrhage","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005261","label":"Joint hemorrhage","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000132","label":"Menorrhagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000939","label":"Osteoporosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011891","label":"Post-partum hemorrhage","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030137","label":"Prolonged bleeding following circumcision","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011890","label":"Prolonged bleeding following procedure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006118","label":"Shortening of all distal phalanges of the fingers","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011884","label":"Abnormal umbilical stump bleeding","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001631","label":"Atrial septal defect","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002239","label":"Gastrointestinal hemorrhage","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0004415","label":"Pulmonary artery stenosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Very rare (<4-1%)","criteria":null}]}}