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Acquired and inborn Cbl\u2010related disorders and MTHFR deficiency cause multisystem, often severe disease. Failure to thrive, neurocognitive or psychiatric symptoms, eye disease, bone marrow alterations, microangiopathy and thromboembolic events are characteristic. The recently identified MTHFD1 defect additionally presents with severe immune deficiency. Deficient Cbl\u2010dependent enzymes cause reduced methylation capacity and metabolite toxicity. Further net\u2010effects of perturbed Cbl function or reduced Cbl supply causing oxidative stress, altered cytokine regulation or immune functions are discussed.<\/jats:p>","DOI":"10.1002\/jimd.12012","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:07:55Z","timestamp":1550102875000},"page":"686-705","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["The clinical presentation of cobalamin\u2010related disorders: From acquired deficiencies to inborn errors of absorption and intracellular pathways"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0590-678X","authenticated-orcid":false,"given":"Martina","family":"Huemer","sequence":"first","affiliation":[{"name":"Division of Metabolism and Children's Research Center University Children's Hospital Z\u00fcrich  Z\u00fcrich Switzerland"},{"name":"Department of Paediatrics Landeskrankenhaus Bregenz  Bregenz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias R.","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Center University Children's Hospital Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,13]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12009"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.76"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.afnr.2017.11.005"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1113996"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30288"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9810-3"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-2199-9_17"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.107"},{"key":"e_1_2_15_10_1","volume-title":"GeneReviews\u00ae [Internet]","author":"Manoli I","year":"2016"},{"key":"e_1_2_15_11_1","first-page":"349","article-title":"Vitamin B12 deficiency","volume":"5226","author":"Hunt A","year":"2014","journal-title":"BMJ"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-017-0003-z"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.24.012003.132440"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.055509"},{"issue":"3","key":"e_1_2_15_15_1","first-page":"27","article-title":"Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency","volume":"27","author":"Hannibal L","year":"2016","journal-title":"Front Mol Biosci"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12833"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9991-4"},{"key":"e_1_2_15_18_1","volume-title":"Food and Nutrition Board. 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