{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:58:49Z","timestamp":1777395529169,"version":"3.51.4"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Sengers syndrome (OMIM #<jats:ext-link>212350<\/jats:ext-link>) is a rare autosomal recessive disorder due to mutations in acylglycerol kinase (<jats:italic>AGK<\/jats:italic>) gene. We report two cases that were diagnosed clinically and confirmed genetically. Both infants had typical clinical features characterized by hypertrophic cardiomyopathy, bilateral cataracts, myopathy, and lactic acidosis, and heart failure was the most severe manifestation. Genetic testing of a boy revealed a homozygous pathogenic variant for Sengers syndrome in <jats:italic>AGK<\/jats:italic> (c.1131+2T&amp;gt;C) which was classified as likely pathogenic according to the ACMG guideline; besides, his skeletal muscle biopsy and transmission electron microscope presented obvious abnormity. One girl had compound heterozygous (c.409C&amp;gt;T and c.390G&amp;gt;A) variants of <jats:italic>AGK<\/jats:italic> gene that was identified in the proband and further Sanger sequencing indicated that the parents carried a single heterozygous mutation each. After the administration of \u201ccocktail\u201d therapy including coenzyme Q10, carnitine, and vitamin B complex, as well as ACEI, heart failure and myopathy of the boy were significantly improved and the condition was stable after 1-year follow-up, while the cardiomyopathy of the girl is not progressive but the plasma lactate acid increased significantly. We present the first report of two infants with Sengers syndrome diagnosed via exome sequencing in China.<\/jats:p>","DOI":"10.3389\/fped.2021.639687","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T04:20:33Z","timestamp":1623039633000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Case Report: Two Chinese Infants of Sengers Syndrome Caused by Mutations in AGK Gene"],"prefix":"10.3389","volume":"9","author":[{"given":"Benzhen","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanhui","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangsong","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanzhu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zipu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s13023-014-0119-3","article-title":"Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients","volume":"9","author":"Haghighi","year":"2014","journal-title":"Orphanet J Rare Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.ajhg.2011.12.005","article-title":"Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome","volume":"90","author":"Mayr","year":"2012","journal-title":"Am J Hum Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ymgme.2012.11.282","article-title":"Mitochondrial citrate synthase crystals: novel finding in Sengers syndrome caused by acylglycerol kinase (AGK) mutations","volume":"108","author":"Siriwardena","year":"2013","journal-title":"Mol Genet Metab."},{"key":"B4","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s00431-004-1465-2","article-title":"Congenital hypertrophic cardiomyopathy, cataract, mitochondrial myopathy and defective oxidative phosphorylation in two siblings with Sengers-like syndrome","volume":"163","author":"Morava","year":"2004","journal-title":"Eur J Pediatr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.molcel.2017.06.014","article-title":"Sengers syndrome-associated mitochondrial acylglycerol kinase is a subunit of the human TIM22 protein import complex","volume":"67","author":"Kang","year":"2017","journal-title":"Mol Cell."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1002\/ajmg.a.36392","article-title":"A novel phenotype associated with cutis laxa, abnormal fat distribution, cardiomyopathy and cataract","volume":"164","author":"Van Asbeck","year":"2014","journal-title":"Am J Med Genet A."},{"key":"B7","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1002\/humu.22071","article-title":"Identification of a truncation mutation of acylglycerol kinase (AGK) gene in a novel autosomal recessive cataract locus","volume":"33","author":"Aldahmesh","year":"2012","journal-title":"Hum Mutat."},{"key":"B8","doi-asserted-by":"publisher","first-page":"118ra10","DOI":"10.1126\/scitranslmed.3003310","article-title":"Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing","volume":"4","author":"Calvo","year":"2012","journal-title":"Sci Transl Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1007\/s00431-019-03399-4","article-title":"RAPIDOMICS: rapid genome-wide sequencing in a neonatal intensive care unit-successes and challenges","volume":"178","author":"Elliott","year":"2019","journal-title":"Eur J Pediatr."},{"key":"B10","first-page":"482","article-title":"Infantile cataract, hypertrophic cardiomyopathy and lactic acidosis following minor muscular exertion\u2013a little known metabolic disease","volume":"189","author":"Lalive","year":"1986","journal-title":"Klin Mbl Augenheilk."},{"key":"B11","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/BF01956157","article-title":"A retrospective study of patients with the hereditary syndrome of congenital cataract, mitochondrial myopathy of heart and skeletal muscle and lactic acidosis","volume":"152","author":"van Ekeren","year":"1993","journal-title":"Eur J Pediatr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1007\/s10545-006-0279-y","article-title":"Hypertrophic cardiomyopathy, cataract, developmental delay, lactic acidosis: a novel subtype of 3-methylglutaconic aciduria","volume":"29","author":"Di Rosa","year":"2006","journal-title":"J Inherit Metab Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"140","DOI":"10.4172\/2329-6682.1000140","article-title":"Two novel mutations in the AGK gene: two case reports with Sengers syndrome","volume":"5","author":"Kor","year":"2016","journal-title":"Gene Technol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1007\/s11011-017-0101-6","article-title":"Mutation in the AGK gene in two siblings with unusual Sengers syndrome","volume":"32","author":"Allali","year":"2017","journal-title":"Metab Brain Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3233\/TRD-180020","article-title":"Extending the phenotypic spectrum of Sengers syndrome: congenital lactic acidosis with synthetic liver dysfunction","volume":"3","author":"Beck","year":"2018","journal-title":"Transl Sci Rare Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1080\/15513815.2019.1639089","article-title":"Atypical presentation of Sengers syndrome: a novel mutation revealed with postmortem genetic testing","volume":"39","author":"Guleray","year":"2020","journal-title":"Fetal Pediatr Pathol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"937","DOI":"10.4103\/ija.IJA-436-17","article-title":"Sustained intraoperative bradycardia revealing Sengers syndrome","volume":"61","author":"Zarrouki","year":"2017","journal-title":"Indian J Anaesth."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1016\/0003-4975(95)00529-T","article-title":"Cardiac transplantation for hypertrophic cardiomyopathy associated with Sengers syndrome","volume":"60","author":"Robbins","year":"1995","journal-title":"Ann Thorac Surg."},{"key":"B19","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/BF02725636","article-title":"Sengers disease: a rare association of hypertrophic cardiomyopathy and congenital cataracts","volume":"71","author":"Atiq","year":"2004","journal-title":"Indian J Pediatr."},{"key":"B20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/jhg.2015.114","article-title":"Recent advances in RASopathies","volume":"61","author":"Aoki","year":"2016","journal-title":"J Hum Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1007\/s13311-018-0655-y","article-title":"Pompe disease: from basic science to therapy","volume":"15","author":"Kohler","year":"2018","journal-title":"Neurotherapeutics."},{"key":"B22","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.pediatrneurol.2014.06.023","article-title":"Therapeutic strategies for mitochondrial disorders","volume":"52","author":"Finsterer","year":"2015","journal-title":"Pediatr Neurol."}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.639687\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T04:20:37Z","timestamp":1623039637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.639687\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":22,"alternative-id":["10.3389\/fped.2021.639687"],"URL":"https:\/\/doi.org\/10.3389\/fped.2021.639687","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,7]]},"article-number":"639687"}}