{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:20:28Z","timestamp":1787793628333,"version":"build-2784847793"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFC1005100"],"award-info":[{"award-number":["2019YFC1005100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["Z141107004414036"],"award-info":[{"award-number":["Z141107004414036"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["Z151100003915126"],"award-info":[{"award-number":["Z151100003915126"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The most common disorder of the intracellular cobalamin metabolism pathway is the combined methylmalonic acidemia and homocysteinemia, cblC type (cblC). There is a variation in its clinical spectrum ranging from severe neonatal-onset forms that are highly fatal to later-onset forms which are milder. In this study, the first case of an asymptomatic Chinese woman with a defect in congenital cobalamin (cblC type) metabolism at prenatal diagnosis due to elevated homocysteine level is identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>The proband, a male child born to a 29-year-old G1P0 mother, admitted to local hospital with feeding disorder, intellectual disability, seizures, microcephaly, as well as heterophthalmos. The level of the urine methylmalonic was elevated. Equally found were increased blood propionylcarnitine (C3) and propionylcarnitine\/free carnitine ratio (C3\/C0) and decreased methionine levels. The plasma total homocysteine level was elevated at 101.04 \u03bcmol\/L (normal &amp;lt; 15 \u03bcmol\/L). The clinical diagnosis of combined methylmalonic acidemia and homocysteinemia was supported. Four years later, the mother of the boy married again and came to us for prenatal diagnosis exactly 15 weeks after her last menstrual period. Subsequently, there is an increase in the amniotic fluid methylmalonate. The level of the amniotic fluid total homocysteine was marginally high. A considerably elevated amniotic fluid C3 was equally observed. In addition, there is a respective significant increase in the plasma and urine total homocysteine at 31.96 and 39.35 \u03bcmol\/L. After the sequencing of MMACHC genes, it is found that the boy, a proband carried a homozygous mutation of the <jats:italic>MMACHC<\/jats:italic> at c.658_660delAAG. While the boy's mother, she carries two mutations in <jats:italic>MMACHC<\/jats:italic>: c.658_660delAAG and c.617G&amp;gt;A. The fetus is a carrier of the <jats:italic>MMACHC<\/jats:italic> gene. Following the administration of routine treatment, the mother remained symptom-free in the course of pregnancy, and she gave birth to a healthy boy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Variable and nonspecific symptoms characterized the cblC type of methylmalonic acidemia combined with homocysteinemia. Both biochemical assays and mutation analysis are recommended as crucial complementary techniques.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2023.1124387","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T06:26:21Z","timestamp":1683872781000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Case report: An asymptomatic mother with an inborn error of cobalamin metabolism (cblC) detected through high homocysteine levels during prenatal diagnosis"],"prefix":"10.3389","volume":"10","author":[{"given":"Yu-Peng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Xuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe-Hui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Lu","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Qing","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ya","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Qiu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/jimd.12370","article-title":"Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision","volume":"44","author":"Forny","year":"2021","journal-title":"J Inherit Metab Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1002\/humu.21001","article-title":"Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations","volume":"30","author":"Lerner-Ellis","year":"2009","journal-title":"Hum Mutat."},{"key":"B3","doi-asserted-by":"publisher","first-page":"414","DOI":"10.3760\/cma.j.issn.0578-1310.2018.06.003","article-title":"Heterogeneous phenotypes, genotypes, treatment and prevention of 1 003 patients with methylmalonic acidemia in the mainland of China","volume":"56","author":"Liu","year":"2018","journal-title":"Zhonghua Er Ke Za Zhi."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1177\/7010.2006.00231","article-title":"Clinical and biochemical studies on Chinese patients with methylmalonic aciduria","volume":"21","author":"Yang","year":"2006","journal-title":"J Child Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1186\/s13023-020-01485-7","article-title":"Variable phenotypes and outcomes associated with the MMACHC c609G>A homologous mutation: long term follow-up in a large cohort of cases","volume":"15","author":"He","year":"2020","journal-title":"Orphanet J Rare Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1186\/s13023-019-1268-1","article-title":"Methylmalonic and propionic acidemia among hospitalized pediatric patients: a nationwide report","volume":"14","author":"Jiang","year":"2019","journal-title":"Orphanet J Rare Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1097\/00029330-200802010-00006","article-title":"Prenatal diagnosis of methylmalonic aciduria by analysis of organic acids and total homocysteine in amniotic fluid","volume":"121","author":"Zhang","year":"2008","journal-title":"Chin Med J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0265766","DOI":"10.1371\/journal.pone.0265766","article-title":"Comparing amniotic fluid mass spectrometry assays and amniocyte gene analyses for the prenatal diagnosis of methylmalonic aciduria","volume":"17","author":"Liu","year":"2022","journal-title":"PLoS ONE."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e1838","DOI":"10.1002\/mgg3.1838","article-title":"Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis","volume":"9","author":"Hwang","year":"2021","journal-title":"Mol Genet Genomic Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s13023-021-01762-z","article-title":"Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type","volume":"16","author":"Chen","year":"2021","journal-title":"Orphanet J Rare Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1620\/tjem.188.317","article-title":"Automated metabolic profiling and interpretation of GC\/MS data for organic acidemia screening: a personal computer-based system","volume":"188","author":"Kimura","year":"1999","journal-title":"Tohoku J Exp Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/S0378-3782(00)00053-0","article-title":"Simplified screening for organic acidemia using GC\/MS and dried urine filter paper: a study on neonatal mass screening","volume":"58","author":"Fu","year":"2000","journal-title":"Early Hum Dev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2304","DOI":"10.1056\/NEJMoa025225","article-title":"Screening newborns for inborn errors of metabolism by tandem mass spectrometry","volume":"348","author":"Wilcken","year":"2003","journal-title":"N Engl J Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.ymgme.2009.09.008","article-title":"Newborn screening and early biochemical follow-up in combined methylmalonic aciduria and homocystinuria, cblC type, and utility of methionine as a secondary screening analyte","volume":"99","author":"Weisfeld-Adams","year":"2010","journal-title":"Mol Genet Metab."},{"key":"B15","doi-asserted-by":"publisher","first-page":"S409","DOI":"10.1007\/s10545-010-9202-7","article-title":"Treatment of cobalamin C (cblC) deficiency during pregnancy","volume":"33","author":"Brunel-Guitton","year":"2010","journal-title":"J Inherit Metab Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.ymgme.2013.05.007","article-title":"Clinical and biochemical outcome after hydroxocobalamin dose escalation in a series of patients with cobalamin C deficiency","volume":"109","author":"Matos","year":"2013","journal-title":"Mol Genet Metab."},{"key":"B17","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10545-011-9364-y","article-title":"Combined methylmalonic acidemia and homocystinuria, cblC type. I Clinical presentations, diagnosis and management","volume":"35","author":"Carrillo-Carrasco","year":"2012","journal-title":"J Inherit Metab Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s10545-011-9365-x","article-title":"Combined methylmalonic acidemia and homocystinuria, cblC type. II Complications, pathophysiology, and outcomes","volume":"35","author":"Carrillo-Carrasco","year":"2012","journal-title":"J Inherit Metab Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13023-022-02179-y","article-title":"Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists","volume":"17","author":"Kalantari","year":"2022","journal-title":"Orphanet J Rare Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1007\/s11011-018-0189-3","article-title":"Late-onset cobalamin C deficiency Chinese sibling patients with neuropsychiatric presentations","volume":"33","author":"Wang","year":"2018","journal-title":"Metab Brain Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"896177","DOI":"10.3389\/fped.2022.896177","article-title":"Case report: a case of late-onset combined methylmalonic acidemia and hyperhomocysteinemia induced by a vegetarian diet","volume":"10","author":"Xu","year":"2022","journal-title":"Front Pediatr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.jpeds.2009.06.046","article-title":"Asymptomatic maternal combined homocystinuria and methylmalonic aciduria (cblC) detected through low carnitine levels on newborn screening","volume":"155","author":"Lin","year":"2009","journal-title":"J Pediatr."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e04282","DOI":"10.1002\/ccr3.4282","article-title":"Cobalamin deficiency in pregnancy","volume":"9","author":"Konings","year":"2021","journal-title":"Clin Case Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e1003530","DOI":"10.1371\/journal.pgen.1003530","article-title":"Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets","volume":"9","author":"Grarup","year":"2013","journal-title":"PLoS Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/ng1683","article-title":"Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type","volume":"38","author":"Lerner-Ellis","year":"2006","journal-title":"Nat Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/jhg.2010.81","article-title":"Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria","volume":"55","author":"Liu","year":"2010","journal-title":"J Hum Genet."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2023.1124387\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T06:26:39Z","timestamp":1683872799000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2023.1124387\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,12]]},"references-count":26,"alternative-id":["10.3389\/fnut.2023.1124387"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2023.1124387","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,12]]},"article-number":"1124387"}}