{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:10:36Z","timestamp":1787163036925,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006086","name":"Office of Strategic Coordination","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01HG010218"],"award-info":[{"award-number":["U01HG010218"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01HG007708"],"award-info":[{"award-number":["U01HG007708"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Biallelic pathogenic variants in the\n                    <jats:italic>TANGO2<\/jats:italic>\n                    (transport and Golgi organization 2 homolog) gene have been identified as causing a rare metabolic disorder characterized by susceptibility to recurrent rhabdomyolysis, lactic acidosis, encephalopathy, and life\u2010threatening tachyarrhythmias. Recently published reports suggest variable clinical severity and phenotypes. This study details five new patients from two families with biallelic pathogenic variants in the\n                    <jats:italic>TANGO2<\/jats:italic>\n                    gene identified by whole exome sequencing and includes the largest number of affected individuals from a single family reported to date. We document significant intrafamilial variability and highlight that milder phenotypes may be underrecognized. We present biochemical and clinical data to help highlight the features that aid in consideration of this condition in the differential with disorders of fatty acid oxidation. We also present a comprehensive literature review summarizing the molecular, clinical, and biochemical findings for 92 individuals across 13 publications. Of the 27 pathogenic variants reported to date, the recurrent exons 3\u20139 deletion represents the most common variant seen in 42% of individuals with TANGO2 deficiency. Common clinical features seen in &gt;70% of all individuals include acute metabolic crisis, rhabdomyolysis, neurologic abnormalities, developmental delay, and intellectual disability. Findings such as elevated creatine kinase, hypothyroidism, ketotic hypoglycemia, QT prolongation, or abnormalities of long\u2010chain acylcarnitines and urine dicarboxylic acids should raise clinical suspicion for this life\u2010threatening condition.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62543","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T07:40:29Z","timestamp":1634802029000},"page":"473-487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Variable clinical severity in\n                    <scp>TANGO2<\/scp>\n                    deficiency: Case series and literature review"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7401-0493","authenticated-orcid":false,"given":"Jennifer","family":"Schymick","sequence":"first","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"},{"name":"Department of Pediatrics Santa Clara Valley Health and Hospital System  San Jose California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Leahy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"},{"name":"Cook Children's Medical Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Cowan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"},{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura R. Z.","family":"Ruzhnikov","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"},{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Stanford Center for Undiagnosed Diseases  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Gates","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Stanford Center for Undiagnosed Diseases  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopal","family":"Pramanik","sequence":"additional","affiliation":[{"name":"Stanford Center for Undiagnosed Diseases  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Undiagnosed Diseases Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vamsi","family":"Yarlagadda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Stanford Center for Undiagnosed Diseases  Stanford California USA"},{"name":"Department of Medicine Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5369-346X","authenticated-orcid":false,"given":"Jonathan A.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"},{"name":"Stanford Center for Undiagnosed Diseases  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Enns","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.09.008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04377"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12314"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0137-y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0412-6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.39"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcped.2020.11.004"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12149"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.12.009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.12.008"},{"key":"e_1_2_9_13_1","volume-title":"GeneReviews\u00ae","author":"Leslie N. 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