{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:56:07Z","timestamp":1791212167794,"version":"4.1.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"publisher","award":["022D01D55"],"award-info":[{"award-number":["022D01D55"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1038\/s41390-025-04720-8","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T10:42:32Z","timestamp":1766745752000},"page":"776-781","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Reversible Pulmonary Hypertension in CblC Deficiency (MMACHC c.80\u2009A&gt;G): long-term outcomes of metabolic and PH-targeted therapy"],"prefix":"10.1038","volume":"100","author":[{"given":"Ruxuan","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunying","family":"zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"4720_CR1","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1038\/s41390-024-03581-x","volume":"97","author":"L Hao","year":"2025","unstructured":"Hao, L. et al. Long-term follow-up of Chinese patients with methylmalonic acidemia of the cblC and mut subtypes. Pediatr. Res. 97, 2010\u20132019, https:\/\/doi.org\/10.1038\/s41390-024-03581-x (2025).","journal-title":"Pediatr. Res"},{"key":"4720_CR2","doi-asserted-by":"publisher","first-page":"414","DOI":"10.3760\/cma.j.issn.0578-1310.2018.06.003","volume":"56","author":"Y Liu","year":"2018","unstructured":"Liu, Y. et al. Heterogeneous phenotypes, genotypes, treatment and prevention of 1,003 patients with methylmalonic acidemia in the mainland of China]. Zhonghua Er Ke Za Zhi 56, 414\u2013420, https:\/\/doi.org\/10.3760\/cma.j.issn.0578-1310.2018.06.003 (2018).","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"4720_CR3","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, R. J. & Venditti, C. P. Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management. J. Inherit. Metab. Dis. 35, 91\u2013102, https:\/\/doi.org\/10.1007\/s10545-011-9364-y (2012).","journal-title":"J. Inherit. Metab. Dis."},{"key":"4720_CR4","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. 173, 1707\u20131710 (2014).","journal-title":"Eur. J. Pediatr."},{"key":"4720_CR5","doi-asserted-by":"publisher","first-page":"E540","DOI":"10.1542\/peds.2012-2581","volume":"132","author":"M Komhoff","year":"2013","unstructured":"Komhoff, M. et al. Combined Pulmonary Hypertension and Renal Thrombotic Microangiopathy in Cobalamin C Deficiency. Pediatrics 132, E540\u2013E544, https:\/\/doi.org\/10.1542\/peds.2012-2581 (2013).","journal-title":"Pediatrics"},{"key":"4720_CR6","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/jhg.2010.81","volume":"55","author":"M Liu","year":"2010","unstructured":"Liu, M. et al. Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria. J. Hum. Genet 55, 621\u2013626, https:\/\/doi.org\/10.1038\/jhg.2010.81 (2010).","journal-title":"J. Hum. Genet"},{"key":"4720_CR7","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/jimd.12370","volume":"44","author":"P Forny","year":"2021","unstructured":"Forny, P. et al. Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision. J. Inherit. Metab. Dis. 44, 566\u2013592, https:\/\/doi.org\/10.1002\/jimd.12370 (2021).","journal-title":"J. Inherit. Metab. Dis."},{"key":"4720_CR8","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.echo.2013.02.002","volume":"26","author":"S Lafitte","year":"2013","unstructured":"Lafitte, S. et al. Estimation of pulmonary pressures and diagnosis of pulmonary hypertension by Doppler echocardiography: a retrospective comparison of routine echocardiography and invasive hemodynamics. J. Am. Soc. Echocardiogr. 26, 457\u2013463, https:\/\/doi.org\/10.1016\/j.echo.2013.02.002 (2013).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"4720_CR9","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17, 405\u2013424, https:\/\/doi.org\/10.1038\/gim.2015.30 (2015).","journal-title":"Genet Med"},{"key":"4720_CR10","doi-asserted-by":"publisher","unstructured":"Humbert, M. et al. 2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur. Respir. J. 61, https:\/\/doi.org\/10.1183\/13993003.00879-2022 (2023).","DOI":"10.1183\/13993003.00879-2022"},{"key":"4720_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-024-03021-3","volume":"19","author":"L Arhip","year":"2024","unstructured":"Arhip, L. et al. Late-onset methylmalonic acidemia and homocysteinemia (cblC disease): systematic review. Orphanet J. Rare Dis. 19, 20. https:\/\/doi.org\/10.1186\/s13023-024-03021-3 (2024).","journal-title":"Orphanet J. Rare Dis."},{"key":"4720_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.805599","volume":"13","author":"S Ling","year":"2022","unstructured":"Ling, S. et al. The Follow-Up of Chinese Patients in cblC Type Methylmalonic Acidemia Identified Through Expanded Newborn Screening. Front Genet 13, 805599. https:\/\/doi.org\/10.3389\/fgene.2022.805599 (2022).","journal-title":"Front Genet"},{"key":"4720_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01485-7","volume":"15","author":"R He","year":"2020","unstructured":"He, R. et al. Variable phenotypes and outcomes associated with the MMACHC c.609G>A homologous mutation: long term follow-up in a large cohort of cases. Orphanet J. Rare Dis. 15, 200. https:\/\/doi.org\/10.1186\/s13023-020-01485-7 (2020).","journal-title":"Orphanet J. Rare Dis."},{"key":"4720_CR14","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1002\/ppul.24781","volume":"55","author":"J Liu","year":"2020","unstructured":"Liu, J. et al. Cobalamin C deficiency presenting with diffuse alveolar hemorrhage and pulmonary microangiopathy. Pediatr. Pulmonol. 55, 1481\u20131486, https:\/\/doi.org\/10.1002\/ppul.24781 (2020).","journal-title":"Pediatr. Pulmonol."},{"key":"4720_CR15","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s00467-016-3399-0","volume":"32","author":"BB Beck","year":"2017","unstructured":"Beck, B. B., van Spronsen, F., Diepstra, A., Berger, R. M. F. & Komhoff, M. Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity. Pediatr. Nephrol. 32, 733\u2013741, https:\/\/doi.org\/10.1007\/s00467-016-3399-0 (2017).","journal-title":"Pediatr. Nephrol."},{"key":"4720_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.1109445","volume":"9","author":"D Yuan","year":"2022","unstructured":"Yuan, D. et al. Mechanism of homocysteine-mediated endothelial injury and its consequences for atherosclerosis. Front Cardiovasc Med 9, 1109445. https:\/\/doi.org\/10.3389\/fcvm.2022.1109445 (2022).","journal-title":"Front Cardiovasc Med"},{"key":"4720_CR17","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/nrendo.2014.155","volume":"10","author":"MK Jensen","year":"2014","unstructured":"Jensen, M. K. et al. Novel metabolic biomarkers of cardiovascular disease. Nat. Rev. Endocrinol. 10, 659\u2013672, https:\/\/doi.org\/10.1038\/nrendo.2014.155 (2014).","journal-title":"Nat. Rev. Endocrinol."},{"key":"4720_CR18","doi-asserted-by":"publisher","first-page":"142","DOI":"10.21693\/1933-088x-20.5.142","volume":"20","author":"CL Welch","year":"2021","unstructured":"Welch, C. L. & Chung, W. K. Genomics of Pulmonary Hypertension. Adv. Pulm. Hypertension 20, 142\u2013149, https:\/\/doi.org\/10.21693\/1933-088x-20.5.142 (2021).","journal-title":"Adv. Pulm. Hypertension"},{"key":"4720_CR19","doi-asserted-by":"publisher","first-page":"ii1","DOI":"10.1136\/heartjnl-2015-307792","volume":"102","author":"AE Lammers","year":"2016","unstructured":"Lammers, A. E. et al. Diagnostics, monitoring and outpatient care in children with suspected pulmonary hypertension\/paediatric pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 102, ii1\u2013ii13, https:\/\/doi.org\/10.1136\/heartjnl-2015-307792 (2016).","journal-title":"Heart"},{"key":"4720_CR20","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.1056\/NEJMra2000348","volume":"385","author":"PM Hassoun","year":"2021","unstructured":"Hassoun, P. M. Pulmonary Arterial Hypertension. N. Engl. J. Med 385, 2361\u20132376, https:\/\/doi.org\/10.1056\/NEJMra2000348 (2021).","journal-title":"N. Engl. J. Med"},{"key":"4720_CR21","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.resinv.2018.10.004","volume":"57","author":"A Ogawa","year":"2019","unstructured":"Ogawa, A., Sakao, S., Tanabe, N., Matsubara, H. & Tatsumi, K. Use of vasodilators for the treatment of pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis: A systematic review. Respir. Investig. 57, 183\u2013190, https:\/\/doi.org\/10.1016\/j.resinv.2018.10.004 (2019).","journal-title":"Respir. Investig."}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04720-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04720-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04720-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:33:03Z","timestamp":1791210783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04720-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["4720"],"URL":"https:\/\/doi.org\/10.1038\/s41390-025-04720-8","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]},"assertion":[{"value":"29 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The study was approved by the Institutional Review Board of Beijing Children\u2019s Hospital (approval no. 2024-Y-090-D).","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Consent for publication was obtained from the institution and the patient\u2019s parents.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Ethics"}}]}}