{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:27:57Z","timestamp":1790832477390,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T00:00:00Z","timestamp":1444953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T00:00:00Z","timestamp":1444953600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2016,3]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n The encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria is associated with deficiency of succinate\u2010CoA ligase, caused by mutations in\n SUCLA2<\/jats:italic>\n or\n SUCLG1<\/jats:italic>\n . We report here 25 new patients with succinate\u2010CoA ligase deficiency, and review the clinical and molecular findings in these and 46 previously reported patients.\n <\/jats:p>\n <\/jats:sec>\n \n Patients and results<\/jats:title>\n \n Of the 71 patients, 50 had\n SUCLA2<\/jats:italic>\n mutations and 21 had\n SUCLG1<\/jats:italic>\n mutations. In the newly\u2010reported 20\n SUCLA2<\/jats:italic>\n patients we found 16 different mutations, of which nine were novel: two large gene deletions, a 1 bp duplication, two 1 bp deletions, a 3 bp insertion, a nonsense mutation and two missense mutations. In the newly\u2010reported\n SUCLG1<\/jats:italic>\n patients, five missense mutations were identified, of which two were novel. The median onset of symptoms was two months for patients with\n SUCLA2<\/jats:italic>\n mutations and at birth for\n SUCLG1<\/jats:italic>\n patients. Median survival was 20 years for\n SUCLA2<\/jats:italic>\n and 20 months for\n SUCLG1<\/jats:italic>\n . Notable clinical differences between the two groups were hepatopathy, found in 38 % of\n SUCLG1<\/jats:italic>\n cases but not in\n SUCLA2<\/jats:italic>\n cases, and hypertrophic cardiomyopathy which was not reported in\n SUCLA2<\/jats:italic>\n patients, but documented in 14 % of cases with\n SUCLG1<\/jats:italic>\n mutations. Long survival, to age 20 years or older, was reported in 12 % of\n SUCLA2<\/jats:italic>\n and in 10 % of\n SUCLG1<\/jats:italic>\n patients. The most frequent abnormality on neuroimaging was basal ganglia involvement, found in 69 % of\n SUCLA2<\/jats:italic>\n and 80 % of\n SUCLG1<\/jats:italic>\n patients. Analysis of respiratory chain enzyme activities in muscle generally showed a combined deficiency of complexes I and IV, but normal histological and biochemical findings in muscle did not preclude a diagnosis of succinate\u2010CoA ligase deficiency. In five patients, the urinary excretion of methylmalonic acid was only marginally elevated, whereas elevated plasma methylmalonic acid was consistently found.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n To our knowledge, this is the largest study of patients with\n SUCLA2<\/jats:italic>\n and\n SUCLG1<\/jats:italic>\n deficiency. The most important findings were a significantly longer survival in patients with\n SUCLA2<\/jats:italic>\n mutations compared to\n SUCLG1<\/jats:italic>\n mutations and a trend towards longer survival in patients with missense mutations compared to loss\u2010of\u2010function mutations. Hypertrophic cardiomyopathy and liver involvement was exclusively found in patients with\n SUCLG1<\/jats:italic>\n mutations, whereas epilepsy was much more frequent in patients with\n SUCLA2<\/jats:italic>\n mutations compared to patients with\n SUCLG1<\/jats:italic>\n mutations. The mutation analysis revealed a number of novel mutations, including a homozygous deletion of the entire\n SUCLA2<\/jats:italic>\n gene, and we found evidence of two founder mutations in the Scandinavian population, in addition to the known\n SUCLA2<\/jats:italic>\n founder mutation in the Faroe Islands.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s10545-015-9894-9","type":"journal-article","created":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T05:05:02Z","timestamp":1444971902000},"page":"243-252","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Succinate\u2010CoA ligase deficiency due to mutations in\n SUCLA2<\/i>\n and\n SUCLG1<\/i>\n : phenotype and genotype correlations in 71 patients"],"prefix":"10.1002","volume":"39","author":[{"given":"Rosalba","family":"Carrozzo","sequence":"first","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine Bambino Ges\u00f9 Children's Hospital, IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Verrigni","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine Bambino Ges\u00f9 Children's Hospital, IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnhild","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences for Children Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"de Coo","sequence":"additional","affiliation":[{"name":"Department of Neurology Erasmus Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hernan","family":"Amartino","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda Infantil Hospital Universitario Austral Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine Bambino Ges\u00f9 Children's Hospital, IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Buhas","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Montreal Children's Hospital Montr\u00e9al Queb\u00e9c Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Mesli","sequence":"additional","affiliation":[{"name":"Biochemistry CHU de Bordeaux Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Naess","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Centre for Inherited Metabolic Diseases Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred Peter","family":"Born","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Copenhagen University Hospital Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berit","family":"Woldseth","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Prontera","sequence":"additional","affiliation":[{"name":"Centro di Riferimento Regionale di Genetica Medica Azienda Ospedaliera di Perugia, CREO Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Batbayli","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstine","family":"Ravn","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00f3\u00f0i","family":"Joensen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics National Hospital of the Faroe Islands T\u00f3rshavn Faroe Islands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duccio M.","family":"Cordelli","sequence":"additional","affiliation":[{"name":"U.O. 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