{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:29:49Z","timestamp":1777555789100,"version":"3.51.4"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"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. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Triple A syndrome, caused by autosomal recessively inherited mutations in the <jats:italic>AAAS<\/jats:italic> gene is characterized by alacrima, achalasia, adrenal insufficiency, and neurological impairment. To the best of our knowledge, no patients of both sexes have been reported to have offspring. Our aim was to assess the causes of infertility in male patients with this multisystemic syndrome, and to present a female patient that spontaneously conceived a child.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Cross-sectional study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Six males aged 19-48 years were included. Gonadotropins, testosterone, DHEAS, androstenedione, inhibin B, anti-Mullerian hormone measurements and testicular ultrasound were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All six male patients had impaired general health and neurological symptoms including erectile and ejaculatory dysfunction. None of them had an offspring. The only demonstrated cause of infertility in our male patients was erectile and ejaculatory dysfunction which precludes sexual intercourse. Our patients had normal libido but were sexually abstinent. Except for low adrenal androgen levels, the concentrations of all measured hormones as well as testicular ultrasound were normal which may indicate the possibility of spermatogenesis in male patients with triple A syndrome. Little is known about fertility in female patients, but based on our observations spontaneous pregnancies seem to be possible.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results contribute to still scarce knowledge on fertility in patients with Triple A syndrome and as well represents a foundation for further research on causes of infertility and possible treatment options.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1357084","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:19:12Z","timestamp":1710339552000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Fertility and sexual activity in patients with Triple A syndrome"],"prefix":"10.3389","volume":"15","author":[{"given":"Katja K.","family":"Dumic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudine","family":"Heinrichs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Koehler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Huebner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miroslav","family":"Dumic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vesna","family":"Kusec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Dusek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Quitter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1081\/ERC-200044138","article-title":"The triple A syndrome is due to mutations in ALADIN, a novel member of the nuclear pore complex","volume":"30","author":"Huebner","year":"2004","journal-title":"EndocrRes"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200206106","article-title":"Proteomic analysis of the mammalian nuclear pore complex","volume":"158","author":"Cronshaw","year":"2002","journal-title":"J Cell Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.083246","article-title":"The nuclear pore complex\u2013structure and function at a glance","volume":"128","author":"Kabachinski","year":"2015","journal-title":"J Cell Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2009.41.6.043","article-title":"Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome","volume":"41","author":"Cho","year":"2009","journal-title":"Exp Mol Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e0124582","DOI":"10.1371\/journal.pone.0124582","article-title":"Role of ALADIN in human adrenocortical cells for oxidative stress response and steroidogenesis","volume":"10","author":"J\u00fchlen","year":"2015","journal-title":"PloS One"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-010-0661-y","article-title":"Intracellular ROS level is increased in fibroblasts of triple A syndrome patients","volume":"88","author":"Kind","year":"2010","journal-title":"J Mol Med (Berl)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1241","article-title":"Deficiency of ALADIN impairs redox homeostasis in human adrenal cells and inhibits steroidogenesis","volume":"154","author":"Prasad","year":"2013","journal-title":"Endocrinology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"103665","DOI":"10.1016\/j.ejmg.2019.05.004","article-title":"Homozygous deletion of the entire AAAS gene in a triple A syndrome patient","volume":"62","author":"Koehler","year":"2019","journal-title":"Eur J Med Genet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1081\/ERC-120016998","article-title":"New insights into the molecular basis of the triple A syndrome","volume":"28","author":"Huebner","year":"2002","journal-title":"EndocrRes"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-010-1314-4","article-title":"Two siblings with triple A syndrome and novel mutation presenting as hereditary polyneuropathy","volume":"170","author":"Dumic","year":"2011","journal-title":"Eur J Pediatr"},{"key":"B11","doi-asserted-by":"publisher","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":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/BF01958757","article-title":"Adrenocorticotropic hormone insensitivity associated with autonomic nervous system disorders","volume":"150","author":"Dumi\u0107","year":"1991","journal-title":"Eur J Pediatr"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/BF01954269","article-title":"Familial adrenocorticotropin unresponsiveness associated with alacrima and achalasia: biochemical and molecular studies in two siblings with clinical heterogeneity","volume":"154","author":"Heinrichs","year":"1995","journal-title":"Eur J Pediatr"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-017-3008-7","article-title":"Testicular adrenal rest tumors in congenital adrenal hyperplasia-cross-sectional study of 51 Croatian male patients","volume":"176","author":"Dumic","year":"2017","journal-title":"Eur J Pediatr"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.5.1879-1887.2006","article-title":"Mice lacking the nuclear pore complex protein ALADIN show female infertility but fail to develop a phenotype resembling human triple A syndrome","volume":"26","author":"Huebner","year":"2006","journal-title":"Mol Cell Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E16-03-0158","article-title":"ALADIN is required for the production of fertile mouse oocytes","volume":"28","author":"Carvalhal","year":"2017","journal-title":"Mol Biol Cell"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-019-01099-2","article-title":"A broad range of symptoms in Allgrove syndrome: single center experience in Southeast Anatolia","volume":"43","author":"Polat","year":"2020","journal-title":"J Endocrinol Invest"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1139\/o05-198","article-title":"Cellular localization of 17 natural mutant variants of ALADIN protein in triple A syndrome - shedding light on an unexpected splice mutation","volume":"84","author":"Krumbholz","year":"2006","journal-title":"BiochemCell Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/BF01972967","article-title":"The \u201c4A\u201d syndrome: adrenocortical insufficiency associated with achalasia, alacrima, autonomic and other neurological abnormalities","volume":"154","author":"Gazarian","year":"1995","journal-title":"Eur J Pediatr"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.19.6.0351","article-title":"Adrenocorticotropin insensitivity syndromes","volume":"19","author":"Clark","year":"1998","journal-title":"Endocr Rev"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1357084\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:19:15Z","timestamp":1710339555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1357084\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":20,"alternative-id":["10.3389\/fendo.2024.1357084"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2024.1357084","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"article-number":"1357084"}}