{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:06:02Z","timestamp":1785323162164,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2010,10,6]],"date-time":"2010-10-06T00:00:00Z","timestamp":1286323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The most common inborn error of cobalamin (cbl) metabolism in China is the cblC type characterized by combined methylmalonic acidemia and hyperhomocysteinemia. The clinical presentation is relatively nonspecific, such as feeding difficulty, recurrent vomiting, hypotonia, lethargy, seizures, progressive developmental delay, and mental retardation, together with anemia and metabolic acidosis. More specific biochemical findings include high levels of propionylcarnitine (C3), free carnitine (C3\/C0), and acetylcarnitine (C3\/C2) measured by tandem mass spectrometry (MS\/MS), elevation of methylmalonic acid (MMA) measured by gas chromatography\u2013mass spectrometry (GC\u2010MS), and increased total homocysteine with normal or decreased methionine. We report on 50 Chinese patients with combined methylmalonic acidemia and hyperhomocysteinemia. Forty\u2010six belonged to the cblC complementation group. Mutation analysis of the<jats:italic> MMACHC<\/jats:italic> gene was performed to characterize the mutational spectrum of cblC deficiency, and 17 different mutations were found. Most were clustered in exons 3 and 4, accounting for 91.3% of all mutant alleles. Two mutations were novel, namely, c.315 C&gt;G (p.Y105X) and c.470 G&gt;C(p.W157S). In terms of genotype\u2013phenotype correlation, the c.609 G&gt;A mutation was associated with early\u2010onset disease when homozygous. Unlike previous reports from other populations, c.609 G&gt;A (p.W203X) was the most frequent cblC mutation detected in our study of Chinese patients #Affecting 51 of 92<jats:italic> MMACHC<\/jats:italic> alleles (55.4%). The high prevalence of this nonsense mutation could have potential therapeutic significance for Chinese cblC patients. Besides traditional approaches consisting of hydroxocobalamin injections, carnitine, betaine, and protein restriction, novel drugs that target premature termination codons may have a role in the future.<\/jats:p>","DOI":"10.1007\/s10545-010-9217-0","type":"journal-article","created":{"date-parts":[[2010,10,5]],"date-time":"2010-10-05T08:15:14Z","timestamp":1286266514000},"page":"435-442","source":"Crossref","is-referenced-by-count":76,"title":["Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China"],"prefix":"10.1002","volume":"33","author":[{"given":"Fei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianshu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatric The first Hospital, Beijing University Beijing 100034 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,10,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31671"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1257-y"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa072200"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042871-200701010-00090"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.07.014"},{"key":"e_1_2_6_8_1","first-page":"325","article-title":"Application of tandem mass spectrometry in diagnosis of organic acidemias","volume":"43","author":"Han LS","year":"2005","journal-title":"Zhonghua Er Ke Za 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