{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:52:32Z","timestamp":1781650352042,"version":"3.54.5"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gray platelet syndrome (GPS) is a rare inherited platelet disorder caused by defective \u03b1-granule biogenesis. Emerging evidence suggests that GPS represents a multisystem disorder with immune and inflammatory manifestations. We report three siblings from a single family with genetically confirmed GPS who presented with lifelong thrombocytopenia and mild to severe bleeding symptoms. Notably, all affected individuals had persistently elevated serum vitamin B12 of unclear etiology. One sibling had concomitant type 1 diabetes mellitus and biopsy confirmed celiac disease. This familial case series highlights the phenotypic heterogeneity of GPS and supports its recognition as a multisystem disorder. The consistent finding of hypercobalaminemia represents a notable but poorly understood feature, while the coexistence of autoimmune disease suggests underlying immune dysregulation related to NBEAL2 deficiency. Gray platelet syndrome may involve metabolic and autoimmune manifestations beyond bleeding. Awareness of these associations is essential for comprehensive evaluation and long-term management of affected patients.<\/jats:p>","DOI":"10.1007\/s00277-026-07007-y","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T02:48:05Z","timestamp":1776134885000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gray platelet syndrome as a multisystem disorder: immune dysregulation, autoimmunity, and metabolic abnormalities"],"prefix":"10.1007","volume":"105","author":[{"given":"Hussam","family":"Alzeerelhouseini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen","family":"Aljunaidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mays","family":"Alhouseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"issue":"23","key":"7007_CR1","doi-asserted-by":"publisher","first-page":"4990","DOI":"10.1182\/blood-2010-05-286534","volume":"116","author":"M Gunay-Aygun","year":"2010","unstructured":"Gunay-Aygun M, Zivony-Elboum Y, Gumruk F et al (2010) Gray platelet syndrome: natural history of a large patient cohort. Blood 116(23):4990\u20135001","journal-title":"Blood"},{"issue":"1","key":"7007_CR2","first-page":"569","volume":"2014","author":"M Gunay-Aygun","year":"2014","unstructured":"Gunay-Aygun M (2014) Autoimmunity and inflammation in gray platelet syndrome. Hematol Am Soc Hematol Educ Program 2014(1):569\u2013576","journal-title":"Hematol Am Soc Hematol Educ Program"},{"issue":"19","key":"7007_CR3","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.1182\/blood-2013-04-499491","volume":"122","author":"WHA Kahr","year":"2013","unstructured":"Kahr WHA, Lo RW, Li L et al (2013) Abnormal megakaryocyte development and immune function in NBEAL2 deficiency. 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QJM 106(6):505\u2013515","journal-title":"QJM"},{"issue":"3","key":"7007_CR8","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1515\/cclm-2012-0545","volume":"51","author":"JF Arendt","year":"2013","unstructured":"Arendt JF, Nexo E (2013) Unexpected high plasma cobalamin: proposal for a diagnostic strategy. Clin Chem Lab Med 51(3):489\u2013496","journal-title":"Clin Chem Lab Med"},{"issue":"17","key":"7007_CR9","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1182\/blood.2019004776","volume":"136","author":"MC Sims","year":"2020","unstructured":"Sims MC, Mayer L, Collins JH et al (2020) Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome. Blood 136(17):1956\u20131967. https:\/\/doi.org\/10.1182\/blood.2019004776","journal-title":"Blood"},{"issue":"4","key":"7007_CR10","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1056\/NEJMc1204070","volume":"367","author":"R Carmel","year":"2012","unstructured":"Carmel R, Agrawal YP (2012) Failures of cobalamin assays in pernicious anemia. N Engl J Med 367(4):385\u2013386","journal-title":"N Engl J Med"},{"issue":"6","key":"7007_CR11","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/j.jtha.2023.03.032","volume":"21","author":"JH Collins","year":"2023","unstructured":"Collins JH, Mayer L, Guerrero Lopez JA (2023) Immune dysregulation, autoimmunity, and granule defects in gray platelet syndrome. J Thromb Haemost 21(6):1409\u20131419. https:\/\/doi.org\/10.1016\/j.jtha.2023.03.032","journal-title":"J Thromb Haemost"},{"key":"7007_CR12","first-page":"3253411","volume":"2025","author":"M Takhman","year":"2025","unstructured":"Takhman M, Hattab M, Shihab R, Sarama A, Mosleh S (2025) Unveiling the Gray: A Rare Case of Gray Platelet Syndrome With Hepatomegaly and Immune Dysregulation in a 14-Year-Old. Case Rep Hematol 2025:3253411","journal-title":"Case Rep Hematol"},{"issue":"21","key":"7007_CR13","doi-asserted-by":"publisher","first-page":"2751","DOI":"10.2169\/internalmedicine.4912-20","volume":"59","author":"K Ido","year":"2020","unstructured":"Ido K, Nakane T, Tanizawa N et al (2020) Acquired Gray Platelet Syndrome Associated with Primary Myelofibrosis. 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A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent"}},{"value":"Dr. Hussam Alzeerelhouseini.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Guarantor"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"242"}}