{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:09:48Z","timestamp":1793736588148,"version":"4.6.1"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T00:00:00Z","timestamp":1705708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T00:00:00Z","timestamp":1705708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Combined methylmalonic acidemia and homocystinuria, cblC type is an inborn error of intracellular cobalamin metabolism and the most common one. The age of onset ranges from prenatal to adult. The disease is characterised by an elevation of methylmalonic acid (MMA) and homocysteine and a decreased production of methionine. The aim is to review existing scientific literature of all late onset cblC patients in terms of clinical symptoms, diagnosis, and outcome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A bibliographic database search was undertaken in PubMed (MEDLINE) complemented by a reference list search. We combined search terms regarding cblC disease and late onset. Two review authors performed the study selection, data extraction and quality assessment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Of the sixty-five articles included in this systematic review, we collected a total of 199 patients. The most frequent clinical symptoms were neuropathy\/myelopathy, encephalopathy, psychiatric symptoms, thrombotic microangiopathy, seizures, kidney disease, mild to severe pulmonary hypertension with heart failure and thrombotic phenomena. There were different forms of supplementation used in the different studies collected and, within these studies, some patients received several treatments sequentially and\/or concomitantly. The general outcome was: 64 patients recovered, 78 patients improved, 4 patients did not improve, or the disease progressed, and 12 patients died.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Most scientific literature regarding the late onset cblC disease comes from case reports and case series. In most cases treatment initiation led to an improvement and even recovery of some patients. The lack of complete recovery underlines the necessity for increased vigilance in unclear clinical symptoms for cblC disease.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03021-3","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T09:02:18Z","timestamp":1705741338000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Late-onset methylmalonic acidemia and homocysteinemia (cblC disease): systematic review"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-7844","authenticated-orcid":false,"given":"Loredana","family":"Arhip","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Brox-Torrecilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Motilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Serrano-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Migu\u00e9lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Cuerda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,20]]},"reference":[{"issue":"1","key":"3021_CR1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10545-011-9364-y","volume":"35","author":"N Carrillo-Carrasco","year":"2012","unstructured":"Carrillo-Carrasco N, Chandler RJ, Venditti CP. Combined methylmalonic acidemia and homocystinuria, cblC type: I: clinical presentations, diagnosis and management. J Inherit Metab Dis. 2012;35(1):91\u2013102. https:\/\/doi.org\/10.1007\/s10545-011-9364-y.","journal-title":"J Inherit Metab Dis"},{"key":"3021_CR2","unstructured":"Sloan JL, Carrillo N, Adams D, Venditti CP. Disorders of Intracellular Cobalamin Metabolism. 2008 Feb 25 [updated 2021 Dec 16]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132022."},{"issue":"1","key":"3021_CR3","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/ng1683","volume":"38","author":"JP Lerner-Ellis","year":"2006","unstructured":"Lerner-Ellis JP, Tirone JC, Pawelek PD, Dor\u00e9 C, Atkinson JL, Watkins D, et al. Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. Nat Genet. 2006;38(1):93\u2013100. https:\/\/doi.org\/10.1038\/ng1683.","journal-title":"Nat Genet"},{"key":"3021_CR4","unstructured":"The PRISMA statement for reporting systematic reviews and meta-analyses. Available online, https:\/\/www.prisma-statement.org\/. Accessed 8 Feb 2021."},{"key":"3021_CR5","unstructured":"International database of prospectively registered systematic reviews (PROSPERO). Available online, https:\/\/www.crd.york.ac.uk\/PROSPERO\/. Accessed 8 Feb 2021."},{"key":"3021_CR6","unstructured":"The CARE guidelines. Available online, https:\/\/www.care-statement.org\/. Accessed 8 Feb 2021."},{"key":"3021_CR7","doi-asserted-by":"publisher","first-page":"2794060","DOI":"10.1155\/2017\/2794060","volume":"2017","author":"G Ardissino","year":"2017","unstructured":"Ardissino G, Perrone M, Tel F, Testa S, Morrone A, Possenti I, et al. Late onset cobalamin disorder and hemolytic uremic syndrome: a rare cause of nephrotic syndrome. Case Rep Pediatr. 2017;2017:2794060. https:\/\/doi.org\/10.1155\/2017\/2794060.","journal-title":"Case Rep Pediatr"},{"issue":"6","key":"3021_CR8","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1023\/a:1005508620919","volume":"22","author":"P Augoustides-Savvopoulou","year":"1999","unstructured":"Augoustides-Savvopoulou P, Mylonas I, Sewell AC, Rosenblatt DS. Reversible dementia in an adolescent with cblC disease: clinical heterogeneity within the same family. J Inherit Metab Dis. 1999;22(6):756\u20138. https:\/\/doi.org\/10.1023\/a:1005508620919.","journal-title":"J Inherit Metab Dis"},{"key":"3021_CR9","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/8904_2013_225","volume":"11","author":"PH Backe","year":"2013","unstructured":"Backe PH, Ytre-Arne M, R\u00f8hr AK, Brodtkorb E, Fowler B, Rootwelt H, et al. Novel deletion mutation identified in a patient with late-onset combined methylmalonic acidemia and homocystinuria, cblC type. JIMD Rep. 2013;11:79\u201385. https:\/\/doi.org\/10.1007\/8904_2013_225.","journal-title":"JIMD Rep"},{"issue":"9","key":"3021_CR10","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1002\/ajmg.a.31671","volume":"143A","author":"TI Ben-Omran","year":"2007","unstructured":"Ben-Omran TI, Wong H, Blaser S, Feigenbaum A. Late-onset cobalamin-C disorder: a challenging diagnosis. Am J Med Genet A. 2007;143A(9):979\u201384. https:\/\/doi.org\/10.1002\/ajmg.a.31671.","journal-title":"Am J Med Genet A"},{"issue":"8","key":"3021_CR11","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1212\/wnl.56.8.1113","volume":"56","author":"OA Bodamer","year":"2001","unstructured":"Bodamer OA, Rosenblatt DS, Appel SH, Beaudet AL. Adult-onset combined methylmalonic aciduria and homocystinuria (cblC). Neurology. 2001;56(8):1113. https:\/\/doi.org\/10.1212\/wnl.56.8.1113.","journal-title":"Neurology"},{"issue":"8","key":"3021_CR12","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1212\/01.WNL.0000158476.74580.A8","volume":"64","author":"AL Boxer","year":"2005","unstructured":"Boxer AL, Kramer JH, Johnston K, Goldman J, Finley R, Miller BL. Executive dysfunction in hyperhomocystinemia responds to homocysteine-lowering treatment. Neurology. 2005;64(8):1431\u20134. https:\/\/doi.org\/10.1212\/01.WNL.0000158476.74580.A8.","journal-title":"Neurology"},{"issue":"4","key":"3021_CR13","doi-asserted-by":"publisher","first-page":"871","DOI":"10.20960\/nh.03623","volume":"38","author":"N Brox-Torrecilla","year":"2021","unstructured":"Brox-Torrecilla N, Arhip L, Migu\u00e9lez-Gonz\u00e1lez M, Castellano-Gasch S, Contreras-Chicote A, Rodr\u00edguez-Ferrero ML, et al. Late-onset methylmalonic acidemia and homocysteinemia. Nutr Hosp. 2021;38(4):871\u20135. https:\/\/doi.org\/10.20960\/nh.03623.","journal-title":"Nutr Hosp"},{"issue":"10","key":"3021_CR14","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1007\/s00467-002-0895-1","volume":"17","author":"SM Brunelli","year":"2002","unstructured":"Brunelli SM, Meyers KE, Guttenberg M, Kaplan P, Kaplan BS. Cobalamin C deficiency complicated by an atypical glomerulopathy. Pediatr Nephrol. 2002;17(10):800\u20133. https:\/\/doi.org\/10.1007\/s00467-002-0895-1.","journal-title":"Pediatr Nephrol"},{"issue":"5","key":"3021_CR15","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1007\/s10072-020-04756-0","volume":"42","author":"KJ Chang","year":"2021","unstructured":"Chang KJ, Zhao Z, Shen HR, Bing Q, Li N, Guo X, et al. Adolescent\/adult-onset homocysteine remethylation disorders characterized by gait disturbance with\/without psychiatric symptoms and cognitive decline: a series of seven cases. Neurol Sci. 2021;42(5):1987\u201393. https:\/\/doi.org\/10.1007\/s10072-020-04756-0.","journal-title":"Neurol Sci"},{"issue":"11","key":"3021_CR16","doi-asserted-by":"publisher","first-page":"594905","DOI":"10.3389\/fneur.2020.594905","volume":"26","author":"X Chu","year":"2020","unstructured":"Chu X, Meng L, Zhang W, Luo J, Wang Z, Yuan Y. Peripheral nervous system involvement in late-onset cobalamin C disease? Front Neurol. 2020;26(11):594905. https:\/\/doi.org\/10.3389\/fneur.2020.594905.","journal-title":"Front Neurol"},{"issue":"3","key":"3021_CR17","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3109\/13816810.2015.1010736","volume":"36","author":"FT Collison","year":"2015","unstructured":"Collison FT, Xie YA, Gambin T, Jhangiani S, Muzny D, Gibbs R, et al. whole exome sequencing identifies an adult-onset case of methylmalonic aciduria and homocystinuria type C (cblC) with non-syndromic bull\u2019s eye maculopathy. Ophthalmic Genet. 2015;36(3):270\u20135. https:\/\/doi.org\/10.3109\/13816810.2015.1010736.","journal-title":"Ophthalmic Genet"},{"issue":"1","key":"3021_CR18","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1053\/j.ajkd.2013.08.031","volume":"63","author":"E Cornec-Le Gall","year":"2014","unstructured":"Cornec-Le Gall E, Delmas Y, De Parscau L, Doucet L, Ogier H, Benoist JF, et al. Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency. Am J Kidney Dis. 2014;63(1):119\u201323. https:\/\/doi.org\/10.1053\/j.ajkd.2013.08.031.","journal-title":"Am J Kidney Dis"},{"issue":"39","key":"3021_CR19","doi-asserted-by":"publisher","first-page":"e17334","DOI":"10.1097\/MD.0000000000017334","volume":"98","author":"J Cui","year":"2019","unstructured":"Cui J, Wang Y, Zhang H, Cui X, Wang L, Zheng H. Isolated subacute combined degeneration in late-onset cobalamin C deficiency in children: two case reports and literature review. Medicine. 2019;98(39):e17334. https:\/\/doi.org\/10.1097\/MD.0000000000017334.","journal-title":"Medicine"},{"issue":"9","key":"3021_CR20","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1007\/s00467-009-1188-8","volume":"24","author":"JC Davin","year":"2009","unstructured":"Davin JC, Buter N, Groothoff J, van Wijk J, Bouts A, Strain L, et al. Prophylactic plasma exchange in CD46-associated atypical haemolytic uremic syndrome. Pediatr Nephrol. 2009;24(9):1757\u201360. https:\/\/doi.org\/10.1007\/s00467-009-1188-8.","journal-title":"Pediatr Nephrol"},{"issue":"6","key":"3021_CR21","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.jaapos.2008.06.008","volume":"12","author":"C Gerth","year":"2008","unstructured":"Gerth C, Morel CF, Feigenbaum A, Levin AV. Ocular phenotype in patients with methylmalonic aciduria and homocystinuria, cobalamin C type. J AAPOS. 2008;12(6):591\u20136. https:\/\/doi.org\/10.1016\/j.jaapos.2008.06.008.","journal-title":"J AAPOS"},{"issue":"1","key":"3021_CR22","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.jdcr.2017.09.016","volume":"4","author":"RC Gilson","year":"2017","unstructured":"Gilson RC, Wallis L, Yeh J, Gilson RT. Dementia, diarrhea, desquamating shellac-like dermatitis revealing late-onset cobalamin C deficiency. JAAD Case Rep. 2017;4(1):91\u20134. https:\/\/doi.org\/10.1016\/j.jdcr.2017.09.016.","journal-title":"JAAD Case Rep"},{"issue":"1","key":"3021_CR23","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1136\/jnnp.60.1.107","volume":"60","author":"R Gold","year":"1996","unstructured":"Gold R, Bogdahn U, Kappos L, Toyka KV, Baumgartner ER, Fowler B, et al. Hereditary defect of cobalamin metabolism (homocystinuria and methylmalonic aciduria) of juvenile onset. J Neurol Neurosurg Psychiatry. 1996;60(1):107\u20138. https:\/\/doi.org\/10.1136\/jnnp.60.1.107.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"5","key":"3021_CR24","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/0006-2944(70)90080-3","volume":"4","author":"SI Goodman","year":"1970","unstructured":"Goodman SI, Moe PG, Hammond KB, Mudd SH, Uhlendorf BW. Homocystinuria with methylmalonic aciduria: two cases in a sibship. Biochem Med. 1970;4(5):500\u201315. https:\/\/doi.org\/10.1016\/0006-2944(70)90080-3.","journal-title":"Biochem Med"},{"issue":"1","key":"3021_CR25","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1186\/s12884-019-2474-5","volume":"19","author":"E Grandone","year":"2019","unstructured":"Grandone E, Martinelli P, Villani M, Vecchione G, Fischetti L, Leccese A, et al. Prospective evaluation of pregnancy outcome in an Italian woman with late-onset combined homocystinuria and methylmalonic aciduria. BMC Pregnancy Childbirth. 2019;19(1):318. https:\/\/doi.org\/10.1186\/s12884-019-2474-5.","journal-title":"BMC Pregnancy Childbirth"},{"issue":"9997","key":"3021_CR26","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/S0140-6736(15)00076-8","volume":"386","author":"S Grang\u00e9","year":"2015","unstructured":"Grang\u00e9 S, Bekri S, Artaud-Macari E, Francois A, Girault C, Poitou AL, et al. Adult-onset renal thrombotic microangiopathy and pulmonary arterial hypertension in cobalamin C deficiency. Lancet. 2015;386(9997):1011\u20132. https:\/\/doi.org\/10.1016\/S0140-6736(15)00076-8.","journal-title":"Lancet"},{"issue":"3","key":"3021_CR27","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1053\/j.ajkd.2004.12.004","volume":"45","author":"V Guigonis","year":"2005","unstructured":"Guigonis V, Fr\u00e9meaux-Bacchi V, Giraudier S, Favier R, Borderie D, Massy Z, et al. Late-onset thrombocytic microangiopathy caused by cblC disease: association with a factor H mutation. Am J Kidney Dis. 2005;45(3):588\u201395. https:\/\/doi.org\/10.1053\/j.ajkd.2004.12.004.","journal-title":"Am J Kidney Dis"},{"issue":"12","key":"3021_CR28","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1007\/s00431-014-2330-6","volume":"173","author":"M G\u00fcnd\u00fcz","year":"2014","unstructured":"G\u00fcnd\u00fcz M, Ekici F, \u00d6zayd\u0131n E, Ceylaner S, Perez B. Reversible pulmonary arterial hypertension in cobalamin-dependent cobalamin C disease due to a novel mutation in the MMACHC gene. Eur J Pediatr. 2014;173(12):1707\u201310. https:\/\/doi.org\/10.1007\/s00431-014-2330-6.","journal-title":"Eur J Pediatr"},{"issue":"4","key":"3021_CR29","first-page":"425","volume":"26","author":"E Gurkas","year":"2015","unstructured":"Gurkas E, Kartal A, Aydin K, Kucuk\u00e7ongar A, Dilber C, Ceylaner S. Reversible clinical and magnetic resonance imaging findings in late-onset cobalamin c defect. Genet Couns. 2015;26(4):425\u201330.","journal-title":"Genet Couns"},{"issue":"5","key":"3021_CR30","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1007\/s10545-007-0546-6","volume":"30","author":"SG Heil","year":"2007","unstructured":"Heil SG, Hogeveen M, Kluijtmans LA, van Dijken PJ, van de Berg GB, Blom HJ, et al. Marfanoid features in a child with combined methylmalonic aciduria and homocystinuria (CblC type). J Inherit Metab Dis. 2007;30(5):811. https:\/\/doi.org\/10.1007\/s10545-007-0546-6.","journal-title":"J Inherit Metab Dis"},{"issue":"1","key":"3021_CR31","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/jmd2.12087","volume":"51","author":"T Higashimoto","year":"2019","unstructured":"Higashimoto T, Kim AY, Ogawa JT, Sloan JL, Almuqbil MA, Carlson JM, et al. High-dose hydroxocobalamin achieves biochemical correction and improvement of neuropsychiatric deficits in adults with late onset cobalamin C deficiency. JIMD Rep. 2019;51(1):17\u201324. https:\/\/doi.org\/10.1002\/jmd2.12087.","journal-title":"JIMD Rep"},{"issue":"9","key":"3021_CR32","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s13023-014-0161-1","volume":"15","author":"M Huemer","year":"2014","unstructured":"Huemer M, Scholl-B\u00fcrgi S, Hadaya K, Kern I, Beer R, Seppi K, et al. Three new cases of late-onset cblC defect and review of the literature illustrating when to consider inborn errors of metabolism beyond infancy. Orphanet J Rare Dis. 2014;15(9):161. https:\/\/doi.org\/10.1186\/s13023-014-0161-1.","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"3021_CR33","doi-asserted-by":"publisher","first-page":"e248","DOI":"10.1542\/peds.2012-1945","volume":"132","author":"FG Iodice","year":"2013","unstructured":"Iodice FG, Di Chiara L, Boenzi S, Aiello C, Monti L, Cogo P, et al. Cobalamin C defect presenting with isolated pulmonary hypertension. Pediatrics. 2013;132(1):e248\u201351. https:\/\/doi.org\/10.1542\/peds.2012-1945.","journal-title":"Pediatrics"},{"issue":"4","key":"3021_CR34","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.3305\/nh.2015.31.4.8544","volume":"31","author":"I Jim\u00e9nez-Varo","year":"2015","unstructured":"Jim\u00e9nez-Varo I, Bueno-Delgado M, Dios-Fuentes E, Delgado-Pecellin C, Gonz\u00e1lez-Meneses A, Soto-Moreno A, et al. Combinaci\u00f3n de acidemia metilmal\u00f3nica y homocisteinuria; a prop\u00f3sito de un caso [Combined methylmalonic acidemia and homocystinuria; a case report]. Nutr Hosp. 2015;31(4):1885\u20138. https:\/\/doi.org\/10.3305\/nh.2015.31.4.8544.","journal-title":"Nutr Hosp"},{"issue":"6","key":"3021_CR35","first-page":"633","volume":"55","author":"M K\u0131l\u0131\u00e7","year":"2013","unstructured":"K\u0131l\u0131\u00e7 M, \u00d6zg\u00fcl RK, Dursun A, Tokatl\u0131 A, Kalkano\u011flu-Sivri HS, Anlar B, et al. Cobalamin C defect: a patient of late-onset type with homozygous pR132* mutation. Turk J Pediatr. 2013;55(6):633\u20136.","journal-title":"Turk J Pediatr"},{"issue":"7","key":"3021_CR36","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1007\/s00467-015-3110-x","volume":"30","author":"JC Koenig","year":"2015","unstructured":"Koenig JC, Rutsch F, Bockmeyer C, Baumgartner M, Beck BB, Kranz B, et al. Nephrotic syndrome and thrombotic microangiopathy caused by cobalamin C deficiency. Pediatr Nephrol. 2015;30(7):1203\u20136. https:\/\/doi.org\/10.1007\/s00467-015-3110-x.","journal-title":"Pediatr Nephrol"},{"issue":"2","key":"3021_CR37","doi-asserted-by":"publisher","first-page":"e540","DOI":"10.1542\/peds.2012-2581","volume":"132","author":"M K\u00f6mhoff","year":"2013","unstructured":"K\u00f6mhoff M, Roofthooft MT, Westra D, Teertstra TK, Losito A, van de Kar NC, et al. Combined pulmonary hypertension and renal thrombotic microangiopathy in cobalamin C deficiency. Pediatrics. 2013;132(2):e540\u20134. https:\/\/doi.org\/10.1542\/peds.2012-2581.","journal-title":"Pediatrics"},{"issue":"5","key":"3021_CR38","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1016\/j.ekir.2018.05.015","volume":"3","author":"M Lemoine","year":"2018","unstructured":"Lemoine M, Fran\u00e7ois A, Grang\u00e9 S, Rabant M, Ch\u00e2telet V, Cassiman D, et al. Cobalamin C deficiency induces a typical histopathological pattern of renal arteriolar and glomerular thrombotic microangiopathy. Kidney Int Rep. 2018;3(5):1153\u201362. https:\/\/doi.org\/10.1016\/j.ekir.2018.05.015.","journal-title":"Kidney Int Rep"},{"issue":"3","key":"3021_CR39","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1007\/s12519-015-0032-4","volume":"11","author":"QL Li","year":"2015","unstructured":"Li QL, Song WQ, Peng XX, Liu XR, He LJ, Fu LB. Clinical characteristics of hemolytic uremic syndrome secondary to cobalamin C disorder in Chinese children. World J Pediatr. 2015;11(3):276\u201380. https:\/\/doi.org\/10.1007\/s12519-015-0032-4.","journal-title":"World J Pediatr"},{"issue":"6","key":"3021_CR40","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.jpeds.2009.06.046","volume":"155","author":"HJ Lin","year":"2009","unstructured":"Lin HJ, Neidich JA, Salazar D, Thomas-Johnson E, Ferreira BF, Kwong AM, et al. Asymptomatic maternal combined homocystinuria and methylmalonic aciduria (cblC) detected through low carnitine levels on newborn screening. J Pediatr. 2009;155(6):924\u20137. https:\/\/doi.org\/10.1016\/j.jpeds.2009.06.046.","journal-title":"J Pediatr"},{"issue":"4","key":"3021_CR41","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1136\/jnnp-2014-308203","volume":"86","author":"YR Liu","year":"2015","unstructured":"Liu YR, Ji YF, Wang YL, Zhang BA, Fang GY, Wang JT, et al. Clinical analysis of late-onset methylmalonic acidaemia and homocystinuria, cblC type with a neuropsychiatric presentation. J Neurol Neurosurg Psychiatry. 2015;86(4):472\u20135. https:\/\/doi.org\/10.1136\/jnnp-2014-308203.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"3","key":"3021_CR42","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.braindev.2014.06.007","volume":"37","author":"Y Liu","year":"2015","unstructured":"Liu Y, Wang Q, Li X, Ding Y, Song J, Yang Y. First Chinese case of successful pregnancy with combined methylmalonic aciduria and homocystinuria, cblC type. Brain Dev. 2015;37(3):286\u201391. https:\/\/doi.org\/10.1016\/j.braindev.2014.06.007.","journal-title":"Brain Dev"},{"issue":"1","key":"3021_CR43","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13023-017-0610-8","volume":"12","author":"J Liu","year":"2017","unstructured":"Liu J, Peng Y, Zhou N, Liu X, Meng Q, Xu H, et al. Combined methylmalonic acidemia and homocysteinemia presenting predominantly with late-onset diffuse lung disease: a case series of four patients. Orphanet J Rare Dis. 2017;12(1):58. https:\/\/doi.org\/10.1186\/s13023-017-0610-8.","journal-title":"Orphanet J Rare Dis"},{"issue":"6","key":"3021_CR44","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1002\/ppul.24781","volume":"55","author":"J Liu","year":"2020","unstructured":"Liu J, Tang X, Zhou C, Xu H, Yang H, He R, et al. Cobalamin C deficiency presenting with diffuse alveolar hemorrhage and pulmonary microangiopathy. Pediatr Pulmonol. 2020;55(6):1481\u20136. https:\/\/doi.org\/10.1002\/ppul.24781.","journal-title":"Pediatr Pulmonol"},{"issue":"2","key":"3021_CR45","doi-asserted-by":"publisher","first-page":"164","DOI":"10.5414\/CN106829","volume":"77","author":"A Losito","year":"2012","unstructured":"Losito A, Pittavini L, Covarelli C. Thrombotic microangiopathic nephropathy, pulmonary hypertension and nephromegaly: case report of a patient treated with endothelin receptor antagonist. Clin Nephrol. 2012;77(2):164\u201370. https:\/\/doi.org\/10.5414\/CN106829.","journal-title":"Clin Nephrol"},{"issue":"3","key":"3021_CR46","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/s0022-3476(86)80882-4","volume":"108","author":"GA Mitchell","year":"1986","unstructured":"Mitchell GA, Watkins D, Melan\u00e7on SB, Rosenblatt DS, Geoffroy G, Orquin J, et al. Clinical heterogeneity in cobalamin C variant of combined homocystinuria and methylmalonic aciduria. J Pediatr. 1986;108(3):410\u20135. https:\/\/doi.org\/10.1016\/s0022-3476(86)80882-4.","journal-title":"J Pediatr"},{"issue":"1","key":"3021_CR47","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s13730-017-0298-6","volume":"7","author":"D Navarro","year":"2018","unstructured":"Navarro D, Azevedo A, Sequeira S, Ferreira AC, Carvalho F, Fidalgo T, et al. Atypical adult-onset methylmalonic acidemia and homocystinuria presenting as hemolytic uremic syndrome. CEN Case Rep. 2018;7(1):73\u20136. https:\/\/doi.org\/10.1007\/s13730-017-0298-6.","journal-title":"CEN Case Rep"},{"issue":"1","key":"3021_CR48","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1177\/0969141316641149","volume":"24","author":"C Nogueira","year":"2017","unstructured":"Nogueira C, Marc\u00e3o A, Rocha H, Sousa C, Fonseca H, Valongo C, et al. Molecular picture of cobalamin C\/D defects before and after newborn screening era. J Med Screen. 2017;24(1):6\u201311. https:\/\/doi.org\/10.1177\/0969141316641149.","journal-title":"J Med Screen"},{"issue":"3","key":"3021_CR49","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1093\/ckj\/sfx119","volume":"11","author":"TE Petropoulos","year":"2018","unstructured":"Petropoulos TE, Ramirez ME, Granton J, Licht C, John R, Moayedi Y, et al. Renal thrombotic microangiopathy and pulmonary arterial hypertension in a patient with late-onset cobalamin C deficiency. Clin Kidney J. 2018;11(3):310\u20134. https:\/\/doi.org\/10.1093\/ckj\/sfx119.","journal-title":"Clin Kidney J"},{"issue":"1","key":"3021_CR50","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s12882-020-01748-2","volume":"21","author":"C Philipponnet","year":"2020","unstructured":"Philipponnet C, Desenclos J, Brailova M, Aniort J, Kemeny JL, Deville C, et al. Cobalamin c deficiency associated with antifactor h antibody-associated hemolytic uremic syndrome in a young adult. BMC Nephrol. 2020;21(1):96. https:\/\/doi.org\/10.1186\/s12882-020-01748-2.","journal-title":"BMC Nephrol"},{"issue":"22","key":"3021_CR51","doi-asserted-by":"publisher","first-page":"100560","DOI":"10.1016\/j.ymgmr.2019.100560","volume":"7","author":"L Pollini","year":"2020","unstructured":"Pollini L, Tolve M, Nardecchia F, Galosi S, Carducci C, di Carlo E, et al. Multiple sclerosis and intracellular cobalamin defect (MMACHC\/PRDX1) comorbidity in a young male. Mol Genet Metab Rep. 2020;7(22):100560. https:\/\/doi.org\/10.1016\/j.ymgmr.2019.100560.","journal-title":"Mol Genet Metab Rep"},{"issue":"3","key":"3021_CR52","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/ana.78","volume":"49","author":"JM Powers","year":"2001","unstructured":"Powers JM, Rosenblatt DS, Schmidt RE, Cross AH, Black JT, Moser AB, et al. Neurological and neuropathologic heterogeneity in two brothers with cobalamin C deficiency. Ann Neurol. 2001;49(3):396\u2013400.","journal-title":"Ann Neurol"},{"issue":"4","key":"3021_CR53","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.ymgme.2009.07.017","volume":"98","author":"LE Profitlich","year":"2009","unstructured":"Profitlich LE, Kirmse B, Wasserstein MP, Diaz GA, Srivastava S. High prevalence of structural heart disease in children with cblC-type methylmalonic aciduria and homocystinuria. Mol Genet Metab. 2009;98(4):344\u20138. https:\/\/doi.org\/10.1016\/j.ymgme.2009.07.017.","journal-title":"Mol Genet Metab"},{"issue":"6","key":"3021_CR54","doi-asserted-by":"publisher","first-page":"e1709","DOI":"10.1542\/peds.2013-2711","volume":"134","author":"MH Rahmandar","year":"2014","unstructured":"Rahmandar MH, Bawcom A, Romano ME, Hamid R. Cobalamin C deficiency in an adolescent with altered mental status and anorexia. Pediatrics. 2014;134(6):e1709\u201314. https:\/\/doi.org\/10.1542\/peds.2013-2711.","journal-title":"Pediatrics"},{"issue":"10","key":"3021_CR55","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1001\/archneur.60.10.1457","volume":"60","author":"E Roze","year":"2003","unstructured":"Roze E, Gervais D, Demeret S, Ogier-de-Baulny H, Zittoun J, et al. Neuropsychiatric disturbances in presumed late-onset cobalamin C disease. Arch Neurol. 2003;60(10):1457\u201362. https:\/\/doi.org\/10.1001\/archneur.60.10.1457.","journal-title":"Arch Neurol"},{"issue":"7","key":"3021_CR56","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1056\/NEJM198408163110707","volume":"311","author":"S Shinnar","year":"1984","unstructured":"Shinnar S, Singer HS. Cobalamin C mutation (methylmalonic aciduria and homocystinuria) in adolescence: a treatable cause of dementia and myelopathy. N Engl J Med. 1984;311(7):451\u20134. https:\/\/doi.org\/10.1056\/NEJM198408163110707.","journal-title":"N Engl J Med"},{"issue":"6","key":"3021_CR57","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1136\/jnnp.2007.133025","volume":"79","author":"C Thauvin-Robinet","year":"2008","unstructured":"Thauvin-Robinet C, Roze E, Couvreur G, Horellou MH, Sedel F, Grabli D, et al. The adolescent and adult form of cobalamin C disease: clinical and molecular spectrum. J Neurol Neurosurg Psychiatry. 2008;79(6):725\u20138. https:\/\/doi.org\/10.1136\/jnnp.2007.133025.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"20","key":"3021_CR58","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1002\/ajmg.a.31932","volume":"143A","author":"AC Tsai","year":"2007","unstructured":"Tsai AC, Morel CF, Scharer G, Yang M, Lerner-Ellis JP, Rosenblatt DS, et al. Late-onset combined homocystinuria and methylmalonic aciduria (cblC) and neuropsychiatric disturbance. Am J Med Genet A. 2007;143A(20):2430\u20134. https:\/\/doi.org\/10.1002\/ajmg.a.31932.","journal-title":"Am J Med Genet A"},{"issue":"2","key":"3021_CR59","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1002\/ajmg.10499","volume":"111","author":"JL Van Hove","year":"2002","unstructured":"Van Hove JL, Van Damme-Lombaerts R, Gr\u00fcnewald S, Peters H, Van Damme B, Fryns JP, et al. Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy. Am J Med Genet. 2002;111(2):195\u2013201. https:\/\/doi.org\/10.1002\/ajmg.10499.","journal-title":"Am J Med Genet"},{"issue":"1\u20132","key":"3021_CR60","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jns.2012.04.012","volume":"318","author":"X Wang","year":"2012","unstructured":"Wang X, Sun W, Yang Y, Jia J, Li C. A clinical and gene analysis of late-onset combined methylmalonic aciduria and homocystinuria, cblC type. China J Neurol Sci. 2012;318(1\u20132):155\u20139. https:\/\/doi.org\/10.1016\/j.jns.2012.04.012.","journal-title":"China J Neurol Sci"},{"issue":"3","key":"3021_CR61","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1007\/s11011-018-0189-3","volume":"33","author":"SJ Wang","year":"2018","unstructured":"Wang SJ, Yan CZ, Liu YM, Zhao YY. Late-onset cobalamin C deficiency Chinese sibling patients with neuropsychiatric presentations. Metab Brain Dis. 2018;33(3):829\u201335. https:\/\/doi.org\/10.1007\/s11011-018-0189-3.","journal-title":"Metab Brain Dis"},{"issue":"10","key":"3021_CR62","doi-asserted-by":"publisher","first-page":"103713","DOI":"10.1016\/j.ejmg.2019.103713","volume":"62","author":"C Wang","year":"2019","unstructured":"Wang C, Li D, Cai F, Zhang X, Xu X, Liu X, et al. Mutation spectrum of MMACHC in Chinese pediatric patients with cobalamin C disease: a case series and literature review. Eur J Med Genet. 2019;62(10):103713. https:\/\/doi.org\/10.1016\/j.ejmg.2019.103713.","journal-title":"Eur J Med Genet"},{"issue":"15","key":"3021_CR63","doi-asserted-by":"publisher","first-page":"549","DOI":"10.2147\/NDT.S196924","volume":"21","author":"SJ Wang","year":"2019","unstructured":"Wang SJ, Yan CZ, Wen B, Zhao YY. Clinical feature and outcome of late-onset cobalamin C disease patients with neuropsychiatric presentations: a Chinese case series. Neuropsychiatr Dis Treat. 2019;21(15):549\u201355. https:\/\/doi.org\/10.2147\/NDT.S196924.","journal-title":"Neuropsychiatr Dis Treat"},{"issue":"1","key":"3021_CR64","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s13023-019-1058-9","volume":"14","author":"X Wang","year":"2019","unstructured":"Wang X, Yang Y, Li X, Li C, Wang C. Distinct clinical, neuroimaging and genetic profiles of late-onset cobalamin C defects (cb1C): a report of 16 Chinese cases. Orphanet J Rare Dis. 2019;14(1):109. https:\/\/doi.org\/10.1186\/s13023-019-1058-9.","journal-title":"Orphanet J Rare Dis"},{"issue":"10172","key":"3021_CR65","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1016\/S0140-6736(19)30043-1","volume":"393","author":"SJ Wang","year":"2019","unstructured":"Wang SJ, Zhao YY, Yan CZ. Reversible encephalopathy caused by an inborn error of cobalamin metabolism. Lancet. 2019;393(10172):e29. https:\/\/doi.org\/10.1016\/S0140-6736(19)30043-1.","journal-title":"Lancet"},{"issue":"10","key":"3021_CR66","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1007\/s00415-019-09432-8","volume":"266","author":"Y Wei","year":"2019","unstructured":"Wei Y, Zhou Y, Yuan J, Ni J, Qian M, Cui L, et al. Treatable cause of hereditary spastic paraplegia: eight cases of combined homocysteinaemia with methylmalonic aciduria. J Neurol. 2019;266(10):2434\u20139. https:\/\/doi.org\/10.1007\/s00415-019-09432-8.","journal-title":"J Neurol"},{"issue":"6","key":"3021_CR67","doi-asserted-by":"publisher","first-page":"E37","DOI":"10.1002\/mus.26865","volume":"61","author":"Y Wei","year":"2020","unstructured":"Wei Y, Guan Y, Hao H. Late-onset cobalamin C disease presenting with acute progressive polyneuropathy. Muscle Nerve. 2020;61(6):E37\u201340. https:\/\/doi.org\/10.1002\/mus.26865.","journal-title":"Muscle Nerve"},{"issue":"1","key":"3021_CR68","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1186\/s12887-020-02130-9","volume":"20","author":"LY Wen","year":"2020","unstructured":"Wen LY, Guo YK, Shi XQ. Pulmonary hypertension in late-onset methylmalonic aciduria and homocystinemia: a case report. BMC Pediatr. 2020;20(1):243. https:\/\/doi.org\/10.1186\/s12887-020-02130-9.","journal-title":"BMC Pediatr"},{"issue":"4","key":"3021_CR69","doi-asserted-by":"publisher","first-page":"492","DOI":"10.4103\/0366-6999.199826.PMID:28218226","volume":"130","author":"LY Wu","year":"2017","unstructured":"Wu LY, An H, Liu J, Li JY, Han Y, Zhou AH, et al. Manic-depressive psychosis as the initial symptom in adult siblings with late-onset combined methylmalonic aciduria and homocystinemia. Cobalamin C Type Chin Med J. 2017;130(4):492\u20134. https:\/\/doi.org\/10.4103\/0366-6999.199826.PMID:28218226.","journal-title":"Cobalamin C Type Chin Med J"},{"issue":"3","key":"3021_CR70","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1001\/jamaneurol.2017.4527","volume":"75","author":"C Wu","year":"2018","unstructured":"Wu C, Sun Q, Fan D. Serial magnetic resonance imaging changes in a patient with late-onset cobalamin C disease with a misdiagnosis of metachromatic leukodystrophy. JAMA Neurol. 2018;75(3):374\u20135. https:\/\/doi.org\/10.1001\/jamaneurol.2017.4527.","journal-title":"JAMA Neurol"},{"issue":"6","key":"3021_CR71","doi-asserted-by":"publisher","first-page":"ytab251","DOI":"10.1093\/ehjcr\/ytab251","volume":"5","author":"QH Zhao","year":"2021","unstructured":"Zhao QH, Wu WH, Fu LJ, Wang L. Adult-onset hypoxaemia, diffuse lung lesions, and pulmonary hypertension in cobalamin C defect: a case report. Eur Heart J Case Rep. 2021;5(6):ytab251. https:\/\/doi.org\/10.1093\/ehjcr\/ytab251.","journal-title":"Eur Heart J Case Rep"},{"issue":"2","key":"3021_CR72","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/jimd.12041","volume":"42","author":"M Huemer","year":"2019","unstructured":"Huemer M, Diodato D, Martinelli D, Olivieri G, Blom H, Gleich F, et al. Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: data from the E-HOD registry. J Inherit Metab Dis. 2019;42(2):333\u201352. https:\/\/doi.org\/10.1002\/jimd.12041.","journal-title":"J Inherit Metab Dis"},{"issue":"1","key":"3021_CR73","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s10545-016-9991-4","volume":"40","author":"M Huemer","year":"2017","unstructured":"Huemer M, Diodato D, Schwahn B, Schiff M, Bandeira A, Benoist JF, et al. Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency. J Inherit Metab Dis. 2017;40(1):21\u201348. https:\/\/doi.org\/10.1007\/s10545-016-9991-4.","journal-title":"J Inherit Metab Dis"},{"issue":"13","key":"3021_CR74","doi-asserted-by":"publisher","first-page":"7875","DOI":"10.1167\/iovs.15-17857","volume":"56","author":"L Bonafede","year":"2015","unstructured":"Bonafede L, Ficicioglu CH, Serrano L, Han G, Morgan JI, Mills MD, et al. Cobalamin C deficiency shows a rapidly progressing maculopathy with severe photoreceptor and ganglion cell loss. Invest Ophthalmol Vis Sci. 2015;56(13):7875\u201387. https:\/\/doi.org\/10.1167\/iovs.15-17857.","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03021-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03021-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03021-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T09:04:08Z","timestamp":1705741448000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03021-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,20]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3021"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03021-3","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,20]]},"assertion":[{"value":"10 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20"}}