{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:40:13Z","timestamp":1793194813760,"version":"4.5.0"},"reference-count":15,"publisher":"American Academy of Pediatrics (AAP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) and renal thrombotic microangiopathy (rTMA) are rare diseases in childhood, frequently leading to death and end-stage renal disease, respectively. Their combined occurrence has been reported anecdotally. We investigated the clinical, biochemical, and genetic aspects of 5 children with the rare combination of PAH and rTMA. Onset of disease ranged from 1.5 to 14 years of age. The 2 youngest patients presented with concomitant pulmonary and renal disease; in the older patients, PAH was preceded by rTMA from age 2.5 to 7 years. Three patients presenting at \u22643 years of age died of right ventricular failure secondary to progressive PAH. In 2 patients, cobalamin C (cblC) deficiency was diagnosed postmortem. Three patients were treated with hydroxocobalamin; 1 died 2 weeks after diagnosis, 1 patient exhibited progressive pulmonary vasculopathy, and 1 patient is currently in stable condition. cblC deficiency was diagnosed biochemically 2 days to 18 years after initial presentation. Genetic analysis confirmed mutations in MMACHC in all patients; 4 patients were compound heterozygous, with all having base-pair substitutions (G&amp;gt;A or G&amp;gt;T) at nucleotide 276 in addition to frame-shift mutations. One patient had homozygous nonsense mutations of MMACHC. We established cblC deficiency as the denominator in the rare combination of PAH and rTMA in these children. Early recognition of cblC deficiency and vigorous treatment with hydroxocobalamin may beneficially affect the course of this devastating disease.<\/jats:p>","DOI":"10.1542\/peds.2012-2581","type":"journal-article","created":{"date-parts":[[2013,7,8]],"date-time":"2013-07-08T20:28:27Z","timestamp":1373315307000},"page":"e540-e544","source":"Crossref","is-referenced-by-count":80,"title":["Combined Pulmonary Hypertension and Renal Thrombotic Microangiopathy in Cobalamin C Deficiency"],"prefix":"10.1542","volume":"132","author":[{"given":"Martin","family":"K\u00f6mhoff","sequence":"first","affiliation":[{"name":"Department of Paediatric Nephrology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus T.","family":"Roofthooft","sequence":"additional","affiliation":[{"name":"Centre for Congenital Heart Diseases\u2013Paediatric Cardiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dineke","family":"Westra","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, University of Nijmegen, Nijmegen, Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thea K.","family":"Teertstra","sequence":"additional","affiliation":[{"name":"Department of Paediatric Intensive Care, Beatrix Children\u2019s Hospital, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attilio","family":"Losito","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Santa Maria Della Misericordia Hospital, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole C.A.J.","family":"van de Kar","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, University of Nijmegen, Nijmegen, Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.F.","family":"Berger","sequence":"additional","affiliation":[{"name":"Centre for Congenital Heart Diseases\u2013Paediatric Cardiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2013,8,1]]},"reference":[{"issue":"9815","key":"2021120900125747300_B1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0140-6736(11)61621-8","article-title":"Clinical features of paediatric pulmonary hypertension: a registry study.","volume":"379","author":"Berger","year":"2012","journal-title":"Lancet"},{"issue":"1","key":"2021120900125747300_B2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.amjcard.2010.02.023","article-title":"Outcome of pediatric patients with pulmonary arterial hypertension in the era of new medical therapies.","volume":"106","author":"van Loon","year":"2010","journal-title":"Am J Cardiol"},{"issue":"4","key":"2021120900125747300_B3","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1161\/01.CIR.0000153798.78540.87","article-title":"Transforming growth factor-beta receptor mutations and pulmonary arterial hypertension in childhood.","volume":"111","author":"Harrison","year":"2005","journal-title":"Circulation"},{"issue":"3","key":"2021120900125747300_B4","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/MNH.0b013e3283378f25","article-title":"Thrombotic microangiopathy: new insights.","volume":"19","author":"Benz","year":"2010","journal-title":"Curr Opin Nephrol Hypertens"},{"issue":"17","key":"2021120900125747300_B5","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1056\/NEJMra0902814","article-title":"Atypical hemolytic-uremic syndrome.","volume":"361","author":"Noris","year":"2009","journal-title":"N Engl J Med"},{"issue":"8","key":"2021120900125747300_B6","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1007\/s00467-012-2131-y","article-title":"Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics.","volume":"27","author":"Geerdink","year":"2012","journal-title":"Pediatr Nephrol"},{"issue":"1","key":"2021120900125747300_B7","doi-asserted-by":"crossref","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"},{"issue":"1","key":"2021120900125747300_B8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s10545-011-9364-y","article-title":"Combined methylmalonic acidemia and homocystinuria, cblC type. 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