{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T22:32:05Z","timestamp":1788474725703,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100002651","name":"Barth Syndrome Foundation","doi-asserted-by":"publisher","award":["#22\u20103755704"],"award-info":[{"award-number":["#22\u20103755704"]}],"id":[{"id":"10.13039\/100002651","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000923","name":"Silicon Valley Community Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Barth syndrome (BTHS; OMIM 302060) is an ultra\u2010rare, life\u2010limiting genetic disorder characterized by cardiomyopathy, skeletal muscle myopathy, neutropenia, gastrointestinal issues, and fatigue. Formal analyses of survival and clinical progression remain limited. Barth Syndrome Foundation has maintained an intake database (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009502), representing &gt;\u200980% of the known global population, as well as a patient\u2010inputted registry for a subset of individuals (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009162) with up to 11\u2009years of longitudinal outcome data. We estimate the survival curve, identify factors associated with mortality, characterize clinical manifestations over time, and evaluate causes of death. Death disproportionately affected young children, with a 59% transplant\u2010free survival rate for those age &lt;\u20095. The risk of death plateaued between ages 5\u201325 before rising again. Heart transplantation (HR\u2009=\u20090.316, 95% CI: 0.162\u20130.619,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and living in a developed country (HR\u2009=\u20090.109, 95% CI: 0.018\u20130.659,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) were associated with reduced risk of death. Clinical manifestations increased with age, with musculoskeletal\/fatigue (66%) being most frequent. Top causes of death were cardiac\u2010related complications, with cardiomyopathy\/heart failure (51.3%), mostly in young children &lt;\u20095, and arrhythmia\/cardiac arrest (15%). This is the most comprehensive longitudinal assessment of BTHS survival, mortality risk, and clinical manifestation progression. Early childhood is a period of high mortality risk, driven in large part by heart failure. Although risk of death and hospitalizations plateaued between ages 5\u201325, the clinical burden of BTHS increases throughout the lifespan. Our results may guide clinical care, identify time windows for optimal intervention, and help clinicians better recognize BTHS clinical features.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70189","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:20:52Z","timestamp":1777861252000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Survival and Clinical Progression in Barth Syndrome: Insights From the Barth Syndrome Foundation's Database of 502 Affected Individuals"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1623-2676","authenticated-orcid":false,"given":"Kexin","family":"Fu","sequence":"first","affiliation":[{"name":"Biostatistical Collaboration and Consultation Core (BC3), Department of Biostatistics, School of Global Public Health New York University  New York New York USA"},{"name":"Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-7973","authenticated-orcid":false,"given":"Yonglin","family":"Huang","sequence":"additional","affiliation":[{"name":"Barth Syndrome Foundation  Larchmont New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Bowen","sequence":"additional","affiliation":[{"name":"Barth Syndrome Foundation  Larchmont New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"McCurdy","sequence":"additional","affiliation":[{"name":"Barth Syndrome Foundation  Larchmont New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9962-8564","authenticated-orcid":false,"given":"Reina B.","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics New York University Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0956-071X","authenticated-orcid":false,"given":"Colin K. L.","family":"Phoon","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics New York University Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4422-6963","authenticated-orcid":false,"given":"Lindsay","family":"Marjoram","sequence":"additional","affiliation":[{"name":"Barth Syndrome Foundation  Larchmont New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-6203","authenticated-orcid":false,"given":"Alex","family":"Dahlen","sequence":"additional","affiliation":[{"name":"Biostatistical Collaboration and Consultation Core (BC3), Department of Biostatistics, School of Global Public Health New York University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2019.09.074"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u2010510X(83)90209\u20105"},{"key":"e_1_2_12_4_1","volume-title":"GeneReviews","author":"Ferreira C.","year":"1993"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.20517\/jtgg.2024.22"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000472"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2025.109270"},{"key":"e_1_2_12_8_1","unstructured":"U.S. Food and Drug Administration FDA Grants Accelerated Approval to First Treatment for Barth Syndrome 2025 https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010grants\u2010accelerated\u2010approval\u2010first\u2010treatment\u2010barth\u2010syndrome."},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2024.101138"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12453"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2018.020"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315956"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010025\u201009373\u20105"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.110237"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12422"},{"key":"e_1_2_12_16_1","unstructured":"Barth Syndrome Foundation Barth Syndrome Foundation Internal Intake Data 2025."},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20108\u201070"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246\u2010015\u20101260\u2010z"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246\u2010022\u201002846\u20108"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24538"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541\u20100420.2005.00325.x"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1198\/016214504000001538"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/jev014"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2005.10.005"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246\u2010021\u201002695\u2010x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2018.00079"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcu.23252"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20108\u201023"},{"key":"e_1_2_12_29_1","unstructured":"Barth Syndrome Foundation \u201cDo You Know About Barth Syndrome? 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