{"orpha":26,"name":"Methylmalonic acidemia with homocystinuria","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Combined defect in adenosylcobalamin and methylcobalamin synthesis","Methylmalonic aciduria with homocystinuria"],"definition":"A rare inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures. There are four complementation classes of cobalamin defects (cblC, cblD, cblF and cblJ) that are responsible for methylmalonic acidemia - homocystinuria (methylmalonic acidemia - homocystinuria cblC, cblD cblF and cblJ).","note":null,"url":"https://raremap.alftech.space/d/ORPHA-26/","orphanet_url":"https://www.orpha.net/en/disease/detail/26","names":{"fr":{"name":"Acidémie méthylmalonique avec homocystinurie","synonyms":["Acidurie méthylmalonique avec homocystinurie","Déficit combiné de synthèse de l'adénosylcobalamine et de la méthylcobalamine"],"definition":"Erreur innée rare du métabolisme de la vitamine B12 (cobalamine) caractérisée par une anémie mégaloblastique, une léthargie, un retard de croissance staturo-pondérale, un retard de développement, une déficience intellectuelle et une épilepsie. Il existe quatre&nbsp;classes de complémentation de déficit en cobalamine (cblC, cblD, cblF et cblJ) responsables de l'acidémie méthylmalonique avec homocystinurie (AMH), à savoir acidémie méthylmalmonique - homocystinurie cblC, cblD, cblF et cblJ."},"de":{"name":"Methylmalonazidämie mit Homocystinurie","synonyms":["Kombinierter Defekt der Adenosylcobalamin und Methylcobalamin-Synthese","Methylmalonacidurie - Homocystinurie"],"definition":"Methylmalonazidämie mit Homozystinurie ist ein angeborener Fehler im Vitamin-B12- (Cobalamin-)Stoffwechsel und gekennzeichnet durch Megaloblasten-Anämie, Lethargie, Gedeihstörung, Entwicklungsverzögerung, geistige Behinderung und Krampfanfälle. Es gibt vier Komplementierungsklassen von Cobalaminstörungen (cblC, cblD, cblF und cb1J), die für die Methylmalonazidämie - Homozystinurie verantwortlich sind (Methylmalon-Azidämie - Homozystinurie cblC, cblD cblF und cblJ; siehe jeweils dort)."},"es":{"name":"Acidemia metilmalónica con homocistinuria","synonyms":["Aciduria metilmalónica con homocistinuria","Defecto combinado en la síntesis de adenosilcobalamina y metilcobalamina"],"definition":"Es un error congénito del metabolismo de la vitamina B12 (cobalamina) caracterizado por anemia megaloblástica, letargo, retraso del crecimiento y del desarrollo, discapacidad intelectual, y convulsiones. Existen 4 grupos de complementación por defectos de la cobalamina (cblC, cblD, cblF y cblJ), asociados a la acidemia metilmalónica - homocistinuria (acidemia metilmalónica con homocistinuria cblC, cblD, cblF y cblJ)."},"it":{"name":"Acidemia metilmalonica con omocistinuria","synonyms":["Aciduria metilmalonica con omocistinuria","Difetto combinato della sintesi dell'adenosilcobalamina e della metilcobalamina","Metilmalonicaciduria - omocistinuria"],"definition":"L'acidemia metilmalonica con omocistinuria è un difetto congenito del metabolismo della vitamina B12 (cobalamina), con anemia megaloblastica, letargia, ritardo della crescita e dello sviluppo, deficit cognitivo e convulsioni. Sono noti 4 gruppi di complementazione per i difetti della cobalamina (<i>cblC</i>, <i>cblD</i>, <i>cblF</i> e <i>cblJ</i>), responsabili dell'acidemia metilmalonica - omocistinuria (acidemia metilmalonica - omocistinuria <i>cblC</i>, D, F e J)."},"nl":{"name":"Methylmalonacidemie met homocystinurie","synonyms":["Gecombineerd defect in adenosylcobalamine- en methylcobalaminesynthese","Methylmalonacidurie met homocystinurie","Methylmalonzuuracidemie met homocystinurie","Methylmalonzuuracidurie met homocystinurie"],"definition":"Een zeldzame, aangeboren afwijking van het vitamine B12 (cobalamine)-metabolisme, gekarakteriseerd door megaloblastische anemie, lethargie, groeifalen, ontwikkelingsachterstand, intellectuele achterstand, en insulten. Er zijn vier complementatieklassen van cobalaminedefecten (cblC, cblD, cblF en cblJ) die verantwoordelijk zijn voor methylmalonacidurie - homocystinurie (methylmalonacidurie - homocystinurie cblC, cblD cblF en cblJ)."},"pt":{"name":"Acidemia metilmalónica com homocistinúria","synonyms":["Acidemia metilmalónica-homocistinúria"],"definition":"Anomalia rara congénita do metabolismo da vitamina B12 (cobalamina) caracterizada por anemia megaloblástica, letargia, atraso nas aquisições, perturbação do desenvolvimento e intelectual, convulsões. Existem quatro classes de complementação de defeitos da cobalamina (cblC, cblD cblF e cblJ) responsáveis pela acidemia metilmalónica - homocistinúria (acidemia metilmalónica - homocistinúria cblC, cblD cblF e cblJ)."},"pl":{"name":"Kwasica metylomalonowa z homocystynurią","synonyms":["Acyduria metylomalonowa z homocystynurią","Łączony defekt w syntezie adenozylokobalaminy i metylkobalaminy"]},"cs":{"name":"Methylmalonová acidémie s homocystinurií","synonyms":["Kombinovaná porucha syntézy adenosylkobalaminu a methylkobalaminu","Methylmalonová acidurie s homocysteinurií"]},"uk":{"name":"Метилмалонова ацидемія з гомоцистинурією","synonyms":["Поєднаний дефект синтезу аденозилкобаламіну та метилкобаламіну","Метилмалоновий ацидоз з гомоцистинурією"],"definition":"A rare inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures. There are four complementation classes of cobalamin defects (cblC, cblD, cblF and cblJ) that are responsible for methylmalonic acidemia - homocystinuria (methylmalonic acidemia - homocystinuria cblC, cblD cblF and cblJ)."},"zh":{"name":"甲基丙二酸血症伴高胱氨酸尿症","synonyms":["腺苷钴胺素和甲基钴胺素合成联合缺陷"]},"tr":{"name":"Homosistinüri ile birlikte metilmalonik asidemi","synonyms":["Homosistinüri ile seyreden metilmalonik asidüri","Adenozilkobalamin ve metilkobalamin sentezinde kombine defekt"]}},"xrefs":[{"source":"OMIM","code":"277380","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"277400","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"277410","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614857","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E71.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C50.E0","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1836722766"},{"source":"MONDO","code":"0016826","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C537359","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5848324","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3579","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79163,"name":"Classic organic aciduria","classifications":[150,156]},{"orpha":98396,"name":"Constitutional megaloblastic anemia due to vitamin B12 metabolism disorder","classifications":[156,194]},{"orpha":79171,"name":"Disorder of cobalamin metabolism and transport","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[{"orpha":79284,"name":"Methylmalonic acidemia with homocystinuria type cblF","type":"Clinical subtype"},{"orpha":79282,"name":"Methylmalonic acidemia with homocystinuria, type cblC","type":"Clinical subtype"},{"orpha":79283,"name":"Methylmalonic acidemia with homocystinuria, type cblD","type":"Clinical subtype"},{"orpha":369955,"name":"Methylmalonic acidemia with homocystinuria, type cblJ","type":"Clinical subtype"},{"orpha":369962,"name":"Methylmalonic acidemia with homocystinuria, type cblX","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"ABCD4","name":"ATP binding cassette subfamily D member 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"22922874[PMID]","hgnc":"68","ensembl":"ENSG00000119688","omim":"603214","loci":["14q24.3"],"via":{"orpha":369955,"name":"Methylmalonic acidemia with homocystinuria, type cblJ"}},{"symbol":"HCFC1","name":"host cell factor C1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24011988[PMID]","hgnc":"4839","ensembl":"ENSG00000172534","omim":"300019","loci":["Xq28"],"via":{"orpha":369962,"name":"Methylmalonic acidemia with homocystinuria, type cblX"}},{"symbol":"LMBRD1","name":"LMBR1 domain containing 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301503[PMID]","hgnc":"23038","ensembl":"ENSG00000168216","omim":"612625","loci":["6q13"],"via":{"orpha":79284,"name":"Methylmalonic acidemia with homocystinuria type cblF"}},{"symbol":"MMACHC","name":"metabolism of cobalamin associated C","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"16311595[PMID]_21497120[PMID]","hgnc":"24525","ensembl":"ENSG00000132763","omim":"609831","loci":["1p34.1"],"via":{"orpha":79282,"name":"Methylmalonic acidemia with homocystinuria, type cblC"}},{"symbol":"MMADHC","name":"metabolism of cobalamin associated D","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301409[PMID]_20301503[PMID]","hgnc":"25221","ensembl":"ENSG00000168288","omim":"611935","loci":["2q23.2"],"via":{"orpha":79283,"name":"Methylmalonic acidemia with homocystinuria, type cblD"}}],"inheritance":["Autosomal recessive","X-linked recessive"],"onset":["All ages"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":500.0,"area":"Worldwide","status":"Validated","source":"16714133[PMID]_[EXPERT]"},{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0000646","label":"Amblyopia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012378","label":"Fatigue","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001980","label":"Megaloblastic bone marrow","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000488","label":"Retinopathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030680","label":"Abnormal cardiovascular system morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100022","label":"Abnormality of movement","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000238","label":"Hydrocephalus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000988","label":"Skin rash","frequency":"Occasional (29-5%)","criteria":null}]}}