{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:02:27Z","timestamp":1756339347700,"version":"3.44.0"},"reference-count":24,"publisher":"BMJ","issue":"11","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2024,11,5]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>Triple A syndrome is a rare autosomal recessive disorder presenting as adrenal insufficiency, achalasia and alacrima, often accompanied by neurological complications. We present the cases of two siblings, a girl (patient 1) and a boy (patient 2) in their early adolescence, born from a consanguineous marriage. At the age of 4, patient 1 developed progressive dysphagia when consuming both solid and liquid foods, while patient 2 began displaying abnormal gait by 2 years. Both siblings were confirmed to have alacrima and achalasia. Endocrinological assessments unveiled adrenal insufficiency and resistance to adrenocorticotropin hormone, and genetic analysis revealed a homozygous pathogenic variant of the achalasia-adrenal insufficiency-alacrima syndrome gene. Clinical suspicion of triple A syndrome and early investigation on onset of alacrima are essential for prompt diagnosis and management.<\/jats:p>","DOI":"10.1136\/bcr-2024-260582","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T03:27:14Z","timestamp":1732678034000},"page":"e260582","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Two siblings with triple A syndrome"],"prefix":"10.1136","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4228-7372","authenticated-orcid":false,"given":"Swaraj","family":"Waddankeri","sequence":"first","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Medicine, Mahadevappa Rampure Medical College, Kalaburagi, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0561-9462","authenticated-orcid":false,"given":"Meenakshi","family":"Waddankeri","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Mahadevappa Rampure Medical College, Kalaburagi, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9605-848X","authenticated-orcid":false,"given":"Kshitij","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mahadevappa Rampure Medical College, Kalaburagi, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"2025082623352571000_17.11.e260582.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)91268-0"},{"key":"2025082623352571000_17.11.e260582.2","doi-asserted-by":"publisher","DOI":"10.1530\/EC-17-0255"},{"key":"2025082623352571000_17.11.e260582.3","doi-asserted-by":"publisher","DOI":"10.1007\/BF01972967"},{"key":"2025082623352571000_17.11.e260582.4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.12.2061"},{"key":"2025082623352571000_17.11.e260582.5","doi-asserted-by":"publisher","DOI":"10.1038\/81642"},{"key":"2025082623352571000_17.11.e260582.6","doi-asserted-by":"crossref","first-page":"703","DOI":"10.12659\/AJCR.899546","article-title":"Alacrima as a Harbinger of Adrenal Insufficiency in a Child with Allgrove (AAA) Syndrome","volume":"17","author":"Brown","year":"2016","journal-title":"Am J Case Rep"},{"key":"2025082623352571000_17.11.e260582.7","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2003.00070.x"},{"key":"2025082623352571000_17.11.e260582.8","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.cca.2020.01.029","article-title":"Adrenal insufficiency: Physiology, clinical presentation and diagnostic challenges","volume":"505","author":"Martin-Grace","year":"2020","journal-title":"Clin Chim Acta"},{"key":"2025082623352571000_17.11.e260582.9","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00431-017-3068-8","article-title":"Clinical and genetic characterisation of a series of patients with triple A syndrome","volume":"177","author":"Kurnaz","year":"2018","journal-title":"Eur J Pediatr"},{"key":"2025082623352571000_17.11.e260582.10","doi-asserted-by":"crossref","DOI":"10.1186\/1824-7288-39-39","article-title":"Triple A (Allgrove) syndrome: an unusual association with syringomyelia","volume":"39","author":"Bizzarri","year":"2013","journal-title":"Ital J Pediatr"},{"key":"2025082623352571000_17.11.e260582.11","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2001.600201.x"},{"key":"2025082623352571000_17.11.e260582.12","unstructured":"National Center for Biotechnology Information . ClinVar. Available: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/VCV000005044.10\/ [Accessed 18 Feb 2024]."},{"key":"2025082623352571000_17.11.e260582.13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2147\/PHMT.S173081","article-title":"Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach","volume":"10","author":"Flokas","year":"2019","journal-title":"Pediatric Health Med Ther"},{"key":"2025082623352571000_17.11.e260582.14","doi-asserted-by":"crossref","DOI":"10.1186\/s13023-023-02763-w","article-title":"SCARB1 downregulation in adrenal insufficiency with Allgrove syndrome","volume":"18","author":"Bitetto","year":"2023","journal-title":"Orphanet J Rare Dis"},{"key":"2025082623352571000_17.11.e260582.15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4103\/ijpd.ijpd_155_21","article-title":"Triple-A syndrome: A rare cause of addisonian pigmentation","volume":"23","author":"Dhar","year":"2022","journal-title":"Indian J Paediatr Dermatol"},{"key":"2025082623352571000_17.11.e260582.16","doi-asserted-by":"crossref","first-page":"304","DOI":"10.4103\/0301-4738.33048","article-title":"Triple A syndrome with ophthalmic manifestations in two siblings","volume":"55","author":"Babu","year":"2007","journal-title":"Indian J Ophthalmol"},{"key":"2025082623352571000_17.11.e260582.17","first-page":"161","article-title":"Esophageal achalasia and alacrima in siblings","volume":"43","author":"Singh","year":"2006","journal-title":"Indian Pediatr"},{"key":"2025082623352571000_17.11.e260582.18","doi-asserted-by":"crossref","first-page":"843","DOI":"10.4103\/ijem.IJEM_501_18","article-title":"ACTH resistance syndrome: An experience of three cases","volume":"22","author":"Goyal","year":"2018","journal-title":"Indian J Endocr Metab"},{"key":"2025082623352571000_17.11.e260582.19","doi-asserted-by":"crossref","first-page":"266","DOI":"10.4103\/0972-2327.112494","article-title":"A case of late-onset allgrove syndrome presenting with predominant autonomic dysfunction","volume":"16","author":"Sanyal","year":"2013","journal-title":"Ann Indian Acad Neurol"},{"key":"2025082623352571000_17.11.e260582.20","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.74.5.654"},{"key":"2025082623352571000_17.11.e260582.21","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1007\/s00431-012-1745-1","article-title":"Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome","volume":"171","author":"Dumic","year":"2012","journal-title":"Eur J Pediatr"},{"key":"2025082623352571000_17.11.e260582.22","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2024.1357084","article-title":"Fertility and sexual activity in patients with Triple A syndrome","volume":"15","author":"Dumic","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2025082623352571000_17.11.e260582.23","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1710"},{"key":"2025082623352571000_17.11.e260582.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13492-7"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2024-260582","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T06:35:36Z","timestamp":1756276536000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2024-260582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":24,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,26]]},"published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1136\/bcr-2024-260582"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2024-260582","relation":{},"ISSN":["1757-790X"],"issn-type":[{"type":"electronic","value":"1757-790X"}],"subject":[],"published":{"date-parts":[[2024,11]]}}}