{"orpha":391665,"name":"Homozygous familial hypercholesterolemia","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["HoFH"],"definition":"A rare disorder of lipid metabolism characterized by severely elevated plasma total cholesterol, low-density lipoprotein (LDL) cholesterol levels, and subsequent premature formation of atherosclerotic plaques in the coronary arteries, proximal aorta, and other arteries, significantly increasing the risk of premature cardiovascular disease and death. Xanthomas of the skin and in tendons are also a hallmark of the disease. Lethality is high due to early complications, in particular myocardial infarction and aortic valvular disease.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-391665/","orphanet_url":"https://www.orpha.net/en/disease/detail/391665","names":{"fr":{"name":"Hypercholestérolémie familiale homozygote","synonyms":["HoFH"],"definition":"Trouble rare du métabolisme des lipides caractérisé par des taux très élevés de cholestérol à lipoprotéines de basse densité (LDL) donnant lieu à la formation prématurée de plaques d'athérome dans les artères coronaires, l'aorte proximale et dans d'autres artères, augmentant considérablement le risque de maladie cardiovasculaire à un âge précoce. La maladie se caractérise par ailleurs par des xanthomes cutanés et tendineux. Le taux de décès est élevé en raison des complications survenant à un âge précoce, en particulier de l'infarctus du myocarde et de la valvulopathie aortique."},"de":{"name":"Familiäre Hypercholesterinämie bei homozygoter Mutation","synonyms":["HoFH"],"definition":"Eine seltene Störung des Fettstoffwechsels, die durch einen stark erhöhten Gesamtcholesterinspiegel im Plasma, Low-Density-Lipoprotein (LDL)-Cholesterinspiegel und die anschließende vorzeitige Bildung atherosklerotischer Plaques in den Koronararterien, der proximalen Aorta und anderen Arterien gekennzeichnet ist und das Risiko einer vorzeitigen Herz-Kreislauf-Erkrankung und des Todes deutlich erhöht. Xanthome auf der Haut und in den Sehnen sind ebenfalls ein Kennzeichen der Krankheit. Die Letalität ist aufgrund von Frühkomplikationen, insbesondere Herzinfarkt und Aortenklappenerkrankung, hoch."},"es":{"name":"Hipercolesterolemia familiar homocigota","synonyms":["HoFH"],"definition":"Es un trastorno poco frecuente del metabolismo lipídico caracterizado por niveles marcadamente elevados de colesterol total y de lipoproteínas de baja densidad (LDL) en plasma, con la subsiguiente formación prematura de placas ateroscleróticas en las arterias coronarias, la aorta proximal y otras arterias, lo que aumenta significativamente el riesgo de enfermedad cardiovascular prematura y muerte. Los xantomas de la piel y en los tendones son también una característica distintiva de la enfermedad. La letalidad es alta debido a complicaciones tempranas; en particular, infarto de miocardio y enfermedad de la válvula aórtica."},"it":{"name":"Ipercolesterolemia familiare omozigote","synonyms":["HoFH"],"definition":"Si tratta di una malattia rara del metabolismo dei lipidi, caratterizzata da livelli molto elevati di colesterolo, delle lipoproteine a bassa densità e dalla conseguente formazione precoce di placche aterosclerotiche nelle arterie coronarie, nell'aorta prossimale e in altre arterie, con un aumento significativo del rischio di malattia cardiovascolare in giovane età. Caratteristici della malattia sono gli xantomi della cute e dei tendini. La letalità è elevata a causa delle complicanze precoci, in particolare l'infarto del miocardio."},"nl":{"name":"Homozygote familiale hypercholesterolemie","synonyms":["HoFH"],"definition":"Een zeldzame aandoening van lipidemetabolisme, gekenmerkt door ernstig verhoogde gehaltes in plasma van totaal cholesterol en lage-densiteit lipoproteïne (LDL)-cholesterol, en daaropvolgende premature vorming van atherosclerotische plaques in kransslagaders, proximale aorta, en andere slagaders, wat de kans op vroegtijdige cardiovasculaire ziekte en sterfte aanzienlijk verhoogt. Xanthomen van huid en in pezen zijn ook een typisch kenmerk van de ziekte. Letaliteit is hoog vanwege vroege complicaties, vooral dan hartinfarct en aandoening van aortaklep."},"pt":{"name":"Hipercolesterolemia familiar homozigótica","synonyms":["HoFH"],"definition":"Doença rara do metabolismo lipídico caracterizada por níveis plasmáticos de colesterol total e de colesterol de lipoproteína de baixa densidade (LDL) muito elevados e subsequente formação prematura de placas ateroscleróticas nas artérias coronárias, aorta proximal e outras artérias, aumentando significativamente o risco de doença cardiovascular prematura e morte. Os xantomas na pele e nos tendões também são uma característica da doença. A letalidade é elevada devido a complicações precoces, em particular enfarte do miocárdio e doença valvular aórtica."},"pl":{"name":"Rodzinna hipercholesterolemia","synonyms":["HoFH"]},"cs":{"name":"Homozygotní familiární hypercholesterolémie","synonyms":["HoFH"]},"uk":{"name":"Гомозиготна сімейна гіперхолестеринемія","synonyms":["HoFH"],"definition":"A rare disorder of lipid metabolism characterized by severely elevated plasma total cholesterol, low-density lipoprotein (LDL) cholesterol levels, and subsequent premature formation of atherosclerotic plaques in the coronary arteries, proximal aorta, and other arteries, significantly increasing the risk of premature cardiovascular disease and death. Xanthomas of the skin and in tendons are also a hallmark of the disease. Lethality is high due to early complications, in particular myocardial infarction and aortic valvular disease."},"zh":{"name":"纯合家族性高胆固醇血症","synonyms":["HoFH"],"definition":"本病是一种罕见的脂质代谢障碍，其特征是低密度脂蛋白胆固醇水平严重升高，随后在冠状动脉、近端主动脉和其他动脉中过早形成动脉粥样硬化斑块，导致早期心血管疾病风险限制增加。皮肤和肌腱的黄色瘤也是本病的标志。由于早期并发症，尤其是心肌梗死，本病致死率很高。"},"tr":{"name":"Homozigot ailesel hiperkolesterolemi","synonyms":["HoFH"]}},"xrefs":[{"source":"OMIM","code":"143890","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"OMIM","code":"144010","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"602247","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"603776","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"603813","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E78.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C80.00","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1525871199"},{"source":"MONDO","code":"0018328","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D000090542","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0342881","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"10416","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10057080","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":97978,"name":"Rare endocrine disease"},"parents":[{"orpha":477811,"name":"Rare hypercholesterolemia","classifications":[150,156,193]}],"children":[],"genes":[{"symbol":"ABCG5","name":"ATP binding cassette subfamily G member 5","gene_type":"gene with protein product","association":"Candidate gene tested in","status":"Not yet assessed","source":"20172523[PMID]","hgnc":"13886","ensembl":"ENSG00000138075","omim":"605459","loci":["2p21"]},{"symbol":"ABCG8","name":"ATP binding cassette subfamily G member 8","gene_type":"gene with protein product","association":"Candidate gene tested in","status":"Not yet assessed","source":"20172523[PMID]","hgnc":"13887","ensembl":"ENSG00000143921","omim":"605460","loci":["2p21"]},{"symbol":"APOB","name":"apolipoprotein B","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24404629[PMID]","hgnc":"603","ensembl":"ENSG00000084674","omim":"107730","loci":["2p24.1"]},{"symbol":"LDLR","name":"low density lipoprotein receptor","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24404629[PMID]","hgnc":"6547","ensembl":"ENSG00000130164","omim":"606945","loci":["19p13.2"]},{"symbol":"LDLRAP1","name":"low density lipoprotein receptor adaptor protein 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"11326085[PMID]","hgnc":"18640","ensembl":"ENSG00000157978","omim":"605747","loci":["1p36.11"]},{"symbol":"PCSK9","name":"proprotein convertase subtilisin/kexin type 9","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24404629[PMID]","hgnc":"20001","ensembl":"ENSG00000169174","omim":"607786","loci":["1p32.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Autosomal recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.5842,"area":"Japan","status":"Validated","source":"21146822[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.3194,"area":"Worldwide","status":"Validated","source":"31947532[PMID]_32439005[PMID]_ORPHANET"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.22,"area":"Spain","status":"Validated","source":"27784735[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.625,"area":"Denmark","status":"Validated","source":"23956253[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.33,"area":"Netherlands","status":"Validated","source":"24585268[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.125,"area":"Germany","status":"Validated","source":"23662069[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2017-02-27","source":"4363406[PMID]_27462068[PMID]_25053660[PMID]_23759795[PMID]_19026292[PMID]_12750110[PMID]_6292899[PMID]","terms":[{"hpo":"HP:0003124","label":"Hypercholesterolemia","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0003077","label":"Hyperlipidemia","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0003141","label":"Increased LDL cholesterol concentration","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0004416","label":"Precocious atherosclerosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0005177","label":"Premature arteriosclerosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:3000062","label":"Abnormal internal carotid artery morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005162","label":"Abnormal left ventricular function","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100261","label":"Abnormal tendon morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001681","label":"Angina pectoris","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012397","label":"Aortic atherosclerosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007201","label":"Cerebral artery atherosclerosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001677","label":"Coronaryartery atherosclerosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002094","label":"Dyspnea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030148","label":"Heart murmur","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001397","label":"Hepatic steatosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000822","label":"Hypertension","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001658","label":"Myocardial infarction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006693","label":"Myocardial steatosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004950","label":"Peripheral arterial stenosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005181","label":"Premature coronary artery atherosclerosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001920","label":"Renal artery stenosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001645","label":"Sudden cardiac death","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002829","label":"Arthralgia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004963","label":"Calcification of the aorta","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001653","label":"Mitral regurgitation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000799","label":"Renal steatosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004381","label":"Supravalvular aortic stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010874","label":"Tendon xanthomatosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000991","label":"Xanthomatosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012373","label":"Abnormal eye physiology","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0012638","label":"Abnormality of nervous system physiology","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0030882","label":"Coronary artery aneurysm","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001138","label":"Optic neuropathy","frequency":"Very rare (<4-1%)","criteria":null}]}}