{"orpha":622,"name":"Homocystinuria without methylmalonic aciduria","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Functional methionine synthase deficiency","Methylcobalamin deficiency"],"definition":"Homocystinuria without methylmalonic aciduria is an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, encephalopathy and, sometimes, developmental delay, and associated with homocystinuria and hyperhomocysteinemia. There are three types of homocystinuria without methylmalonic aciduria; <i>cblE, cblG</i> and <i>cblD-</i>variant 1 (<i>cblD</i>v1).","note":null,"url":"https://raremap.alftech.space/d/ORPHA-622/","orphanet_url":"https://www.orpha.net/en/disease/detail/622","names":{"fr":{"name":"Homocystinurie sans acidurie méthylmalonique","synonyms":["Déficit en méthylcobalamine","Déficit fonctionnel en méthionine synthase"],"definition":"L'homocystinurie sans acidurie méthylmalonique (HSAM) est une erreur innée du métabolisme de la vitamine B12 (cobalamine) caractérisée par une anémie mégaloblastique, une encéphalopathie et parfois un retard de développement associé à une homocystinurie et une hyperhomocysteinémie. Il existe 3 types d' HSAM: <i>cblE, cblG</i> et la variante 1 <i>cblD-</i> (<i>cblD</i>v1)."},"de":{"name":"Homocystinurie ohne Methylmalonazidurie","synonyms":["Methioninsynthase-Mangel, funktioneller","Methylcobalamin-Mangel"],"definition":"Die Homozystinurie ohne Methylmalonazidurie ist ein angeborener Defekt im Stoffwechsel des Vitamins B12 (Cobalamin) und gekennzeichnet durch Megaloblasten-Anämie, Enzephalopathie und manchmal verzögerte Entwicklung. Biochemische Symptome sind Homozystinurie und Hyper-Homozysteinämie. Es existieren 3 Typen der Homozystinurie ohne Methylmalonazidurie: <I>cblE</I>, <I>cblG</I> und <I>cblD</I>-Variante 1 (<I>cblD</I>v1)."},"es":{"name":"Homocistinuria sin aciduria metilmalónica","synonyms":["Deficiencia de metilcobalamina","Deficiencia funcional de metionina sintasa"],"definition":"La homocistinuria sin aciduria metilmalónica es un error congénito del metabolismo de la vitamina B12 (cobalamina) caracterizado por anemia megaloblástica, encefalopatía y, en ocasiones, retraso del desarrollo, asociado con homocistinuria e hiperhomocisteinemia. Existen tres tipos de homocistinuria sin aciduria metilmalónica; <i>cblE, cblG</i> y <i>cblD-</i>variante 1 (<i>cblD</i>v1)."},"it":{"name":"Omocistinuria senza aciduria metilmalonica","synonyms":["Deficit di metilcobalamina","Deficit funzionale di metionina sintasi"],"definition":"L'omocistinuria senza aciduria metilmalonica è un difetto metabolico congenito della vitamina B12 (cobalamina), caratterizzato da anemia megaloblastica, encefalopatia e, a volte, ritardo dello sviluppo, associato a omocistinuria, iperomocistinuria e iperomocisteinemia. Sono noti tre tipi di omocistinuria senza aciduria metilmalonica: <i>cblE, cblG</i> e <i>cblD</i>-variante 1 (<i>cblD</i>v1)."},"nl":{"name":"Homocystinurie zonder methylmalonacidurie","synonyms":["Deficiëntie van methylcobalamine","Functionele deficiëntie van methioninesynthase","Homocystinurie zonder methylmalonzuuracidurie"],"definition":"Homocystinurie zonder methylmalonzuuracidurie is een aangeboren afwijking van vitamine B12 (cobalamine)-metabolisme gekenmerkt door megaloblastische anemie, encefalopathie en soms vertraging in de ontwikkeling, en wordt in verband gebracht met homocystinurie en hyperhomocysteïnemie. Er zijn drie types van homocystinurie zonder methylmalonzuuracidurie; <i>cblE</i>, <i>cblG</i> en <i>cblD-</i>variant 1 (<i>cblD</i>v1)."},"pt":{"name":"Homocistinúria sem acidúria metilmalónica","synonyms":["Deficiência de metilcobalamina","Deficiência funcional de metionina sintetase"],"definition":"Homocistinúria sem acidúria metilmalónica é um erro inato do metabolismo da vitamina B12 (cobalamina) e é caracterizada por anemia megaloblástica, encefalopatia e por vezes atraso do desenvolvimento, associada a homocistinúria e hiperhomocisteinemia. Existem três tipos de homocistinúria sem aciduria metilmalonica; <i> cblE, cblG </ i> e a variante 1 de <i> cblD</ i> (<i> cblD</ i> v1)."},"pl":{"name":"Homocystinuria bez acydurii metylomalonowej","synonyms":["Funkcjonalny Niedobór syntazy metioniny","Niedobór metylokobalaminy"]},"cs":{"name":"Homocystinurie bez methylmalonové acidurie","synonyms":["Deficit methylkobalaminu","Funkční deficit methioninsyntázy"],"definition":"Homocystinurie bez metylmalonové acidurie je vrozená porucha metabolismu vitamínu B12 (kobalaminu) typická megaloblastickou anémií (druh chudokrevnosti), encefalopatií a někdy i opožděním vývoje spojená s homocystinurií (zvýšená hladina homocystinu v moči) a hyperhomocysteinemií (zvýšená hladina homocysteinu v krvi). Existují tři typy homocystinurie bez metylmalonové acidurie: cblE, cblG a cblD-varianta 1 (cblDv1)."},"uk":{"name":"Гомоцистинурія без метилмалонової ацидурії","synonyms":["Функціональна недостатність метіонінсинтетази","Дефіцит метилкобаламіну"],"definition":"Homocystinuria without methylmalonic aciduria is an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, encephalopathy and, sometimes, developmental delay, and associated with homocystinuria and hyperhomocysteinemia. There are three types of homocystinuria without methylmalonic aciduria; <i>cblE, cblG</i> and <i>cblD-</i>variant 1 (<i>cblD</i>v1)."},"zh":{"name":"同型半胱氨酸血症不伴甲基丙二酸尿症","synonyms":["功能性甲硫氨酸合成缺乏症"]},"tr":{"name":"Metilmalonik asidüri ile seyretmeyen homosistinüri","synonyms":["Metilkobalamin eksikliği","Fonksiyonel metiyonin sentaz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"236270","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"250940","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"277410","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E72.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C50.B","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"726186034"},{"source":"MONDO","code":"0018964","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4303479","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"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":79173,"name":"Disorder of methionine cycle and sulfur amino acid metabolism","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]}],"children":[{"orpha":308380,"name":"Methylcobalamin deficiency type cblDv1","type":"Clinical subtype"},{"orpha":2169,"name":"Methylcobalamin deficiency type cblE","type":"Clinical subtype"},{"orpha":2170,"name":"Methylcobalamin deficiency type cblG","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"MMADHC","name":"metabolism of cobalamin associated D","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"18385497[PMID]","hgnc":"25221","ensembl":"ENSG00000168288","omim":"611935","loci":["2q23.2"],"via":{"orpha":308380,"name":"Methylcobalamin deficiency type cblDv1"}},{"symbol":"MTR","name":"5-methyltetrahydrofolate-homocysteine methyltransferase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301503[PMID]","hgnc":"7468","ensembl":"ENSG00000116984","omim":"156570","loci":["1q43"],"via":{"orpha":2170,"name":"Methylcobalamin deficiency type cblG"}},{"symbol":"MTRR","name":"5-methyltetrahydrofolate-homocysteine methyltransferase reductase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301503[PMID]","hgnc":"7473","ensembl":"ENSG00000124275","omim":"602568","loci":["5p15.31"],"via":{"orpha":2169,"name":"Methylcobalamin deficiency type cblE"}}],"inheritance":["Autosomal recessive"],"onset":["All ages"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":73.0,"area":"Worldwide","status":"Validated","source":"[EXPERT]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2026-02-12","source":"25526710[PMID]_34625984[PMID]_20301503[PMID]","terms":[{"hpo":"HP:0002156","label":"Homocystinuria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002329","label":"Drowsiness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","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:0002160","label":"Hyperhomocystinemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001972","label":"Macrocytic anemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000709","label":"Psychosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000488","label":"Retinopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012444","label":"Brain atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000726","label":"Dementia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003658","label":"Hypomethioninemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004372","label":"Reduced consciousness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007663","label":"Reduced visual acuity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000505","label":"Visual impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005575","label":"Hemolytic-uremic syndrome","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002912","label":"Methylmalonic acidemia","frequency":"Excluded (0%)","criteria":null}]}}