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Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20\u00a0years (median age, 12\u00a0years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the\n                      <jats:italic>MMACHC gene in the 56<\/jats:italic>\n                      patients. The top five common variants detected in 112 alleles were c.482G\u2009&gt;\u2009A (36.6%), c.609G\u2009&gt;\u2009A (16.1%), c.658_660delAAG (9.8%), c.80A\u2009&gt;\u2009G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G\u2009&gt;\u2009A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G\u2009&gt;\u2009A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G\u2009&gt;\u2009A and other variants. All the patients showed improvement after metabolic treatment with cobalamin,\n                      <jats:sc>l<\/jats:sc>\n                      -carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin,\n                      <jats:sc>l<\/jats:sc>\n                      -carnitine, and betaine appears to be beneficial.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-022-02471-x","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T01:02:55Z","timestamp":1662080575000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Late-onset cblC deficiency around puberty: a retrospective study of the clinical characteristics, diagnosis, and treatment"],"prefix":"10.1186","volume":"17","author":[{"given":"Zhehui","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqing","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqiu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguang","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijie","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1566-6441","authenticated-orcid":false,"given":"Yanling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"2471_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. 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