{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:55:57Z","timestamp":1790045757849,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,10,18]],"date-time":"2014-10-18T00:00:00Z","timestamp":1413590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>TMEM70 deficiency is the most common nuclear\u2010encoded defect affecting the ATP synthase. In this multicentre retrospective study we characterise the natural history of the disease, treatment and outcome in 48 patients with mutations in <jats:italic>TMEM70<\/jats:italic>. Eleven centers from eight European countries, Turkey and Israel participated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All 27 Roma and eight non\u2010Roma patients were homozygous for the common mutation c.317\u20102A\u2009&gt;\u2009G. Five patients were compound heterozygotes for the common mutation and mutations c.470 T\u2009&gt;\u2009A, c.628A\u2009&gt;\u2009C, c.118_119insGT or c.251delC. Six Arab Muslims and two Turkish patients were homozygous for mutations c.238C\u2009&gt;\u2009T, c.316\u2009+\u20091G\u2009&gt;\u2009T, c.336 T\u2009&gt;\u2009A, c.578_579delCA, c.535C\u2009&gt;\u2009T, c.359delC. Age of onset was neonatal in 41 patients, infantile in six cases and two years in one child. The most frequent symptoms at onset were poor feeding, hypotonia, lethargy, respiratory and heart failure, accompanied by lactic acidosis, 3\u2010methylglutaconic aciduria and hyperammonaemia. Symptoms further included: developmental delay (98 %), hypotonia (95 %), faltering growth (94 %), short stature (89 %), non\u2010progressive cardiomyopathy (89 %), microcephaly (71 %), facial dysmorphism (66 %), hypospadias (50 % of the males), persistent pulmonary hypertension of the newborn (22 %) and Wolff\u2010Parkinson\u2010White syndrome (13 %). One or more acute metabolic crises occurred in 24 surviving children, frequently followed by developmental regression. Hyperammonaemic episodes responded well to infusion with glucose and lipid emulsion, and ammonia scavengers or haemodiafiltration. Ten\u2010year survival was 63 %, importantly for prognostication, no child died after the age of five years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TMEM70 deficiency is a panethnic, multisystemic disease with variable outcome depending mainly on adequate management of hyperammonaemic crises in the neonatal period and early childhood.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-014-9774-8","type":"journal-article","created":{"date-parts":[[2014,10,17]],"date-time":"2014-10-17T07:04:30Z","timestamp":1413529470000},"page":"417-426","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["TMEM70 deficiency: long\u2010term outcome of 48 patients"],"prefix":"10.1002","volume":"38","author":[{"given":"Martin","family":"Magner","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine Charles University in Prague and General University Hospital in Prague Ke Karlovu 2 Prague 2 12808 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Dvorakova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine Charles University in Prague and General University Hospital in Prague Ke Karlovu 2 Prague 2 12808 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marketa","family":"Tesarova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine Charles University in Prague and General University Hospital in Prague Ke Karlovu 2 Prague 2 12808 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Mazurova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine Charles University in Prague and General University Hospital in Prague Ke Karlovu 2 Prague 2 12808 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Hansikova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine Charles University in Prague and General University Hospital in Prague Ke Karlovu 2 Prague 2 12808 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Zahorec","sequence":"additional","affiliation":[{"name":"Cardiac Intensive Care Unit, Pediatric Cardiac Center National Institute of Cardiovascular Diseases Limbova 1 Bratislava 833 51 Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Brennerova","sequence":"additional","affiliation":[{"name":"I. Department of Pediatrics Comenius University Children's Hospital Bratislava, Limbova 1 Bratislava 83340 Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Bzduch","sequence":"additional","affiliation":[{"name":"I. Department of Pediatrics Comenius University Children's Hospital Bratislava, Limbova 1 Bratislava 83340 Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronen","family":"Spiegel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emek Medical Center Rappaport Faculty of Medicine Technion, Haifa, Rabin St. Afula 1810100 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoseph","family":"Horovitz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emek Medical Center Rappaport Faculty of Medicine Technion, Haifa, Rabin St. Afula 1810100 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Mandel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Metabolic Unit, Rambam Medical Center Rappaport Faculty of Medicine POB 9602 Technion Haifa 31906 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma 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