{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T17:10:58Z","timestamp":1754154658588,"version":"3.41.2"},"reference-count":13,"publisher":"Endocrinology Research Centre","issue":"3","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p>Congenital isolated ACTH deficiency (\u0421IAD) is an orphan autosomal recessive disease caused by <jats:italic>\u0422\u0412\u042519<\/jats:italic> (1q24.2) gene pathogenic variants. The article presents two cases with a classic manifestation of the \u0421IAD in neonatal period which were confirmed genetically, one of cases revealed the first described TBX19 gene variant. Despite the appearance of significant symptoms in the newborn period in both patients diagnoses were established at the 8th and 22nd months of life. Clinical manifestations of hypoglycemia were present in both patients: from the 1st day of life (episode of apnoea) in patient \u2116 2 and from 7 months (seizures) in patient \u2116 1. Cholestatic jaundice, hepatomegaly, signs of hepatocyte cytolysis, impaired protein-synthetic liver function were the main manifestations of the disease in 1<jats:sup>st<\/jats:sup> patient. This may indicate non-infectious cholestatic hepatitis. Improvement and gradual normalization of clinical and laboratory symptoms during hydrocortisone therapy confirmed the association of liver damage with hypocortisolemia. 2<jats:sup>nd<\/jats:sup> patient had no signs of cholestasis. Low cortisol levels were observed with reduced or low-normal ACTH, which confirmed central hypocorticism. Genetic study in both patients revealed TBX19 gene pathogenic variants in a homozygous state: c.82C&gt;T(p.Q28X) in patient \u21161, not previously described variant c.469-1G&gt;A in patient \u21162.<\/jats:p>","DOI":"10.14341\/probl13519","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:44:15Z","timestamp":1753371855000},"page":"51-55","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":0,"title":["Two cases of congenital isolated adrenocorticotropic hormone deficiency due to pathogenic variants in TBX19"],"prefix":"10.14341","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7906-7408","authenticated-orcid":true,"given":"Yu. L.","family":"Skorodok","sequence":"first","affiliation":[{"name":"Saint-Petersburg state pediatric medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8784-5224","authenticated-orcid":true,"given":"A. V.","family":"Kozhevnikova","sequence":"additional","affiliation":[{"name":"Saint-Petersburg state pediatric medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1104-7368","authenticated-orcid":true,"given":"E. V.","family":"Plotnikova","sequence":"additional","affiliation":[{"name":"Saint-Petersburg state pediatric medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5409-234X","authenticated-orcid":true,"given":"I. Y.","family":"Ioffe","sequence":"additional","affiliation":[{"name":"Saint-Petersburg state pediatric medical university"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-4841","authenticated-orcid":true,"given":"A. N.","family":"Tiulpakov","sequence":"additional","affiliation":[{"name":"The academician N.P. Bochkov medical and genetic scientific center"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Maudhoo A, Maharaj A, Buonocore F, et al. Missplicing due to a synonymous, T96= exonic substitution in the T-box transcription factor TBX19 resulting in isolated ACTH deficiency. 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Hormones (Athens). 2018;17(2):269-273. doi: https:\/\/doi.org\/10.1007\/s42000-018-0028-2","DOI":"10.1007\/s42000-018-0028-2"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/13519\/10881","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:44:26Z","timestamp":1753371866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/13519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":13,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,7,22]]}},"URL":"https:\/\/doi.org\/10.14341\/probl13519","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"type":"electronic","value":"2308-1430"},{"type":"print","value":"0375-9660"}],"subject":[],"published":{"date-parts":[[2025,7,22]]}}}