{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:49:44Z","timestamp":1760057384400,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Nephrogenic diabetes insipidus (NDI) is defined as the inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron to the antidiuretic hormone, arginine vasopressin. NDI is a heterogeneous rare autosomal dominant or X-linked disease. Objective: We present a family with nephrogenic diabetes affecting three males in two generations. Methods: We report two boys with NDI: a 4-month-old infant who was treated for fever, vomiting, and failure to thrive, and his 10-year-old uncle (the mother\u2019s brother), who was admitted concurrently for consuming 11 L of fluid per day. According to family history, the mother\u2019s sibling passed away at the age of two from severe hypernatremic dehydration. Results: The infant\u2019s clinical and laboratory evaluation revealed a 7.8 mL\/kg\/h urine output, hypernatremic hyperchloremic alkalosis, extremely low urine density (1002), and elevated copeptin level. In contrast, the uncle\u2019s clinical and laboratory evaluation revealed marked polyuria, low urine density, and elevated copeptin, all of which were suggestive of diabetes insipidus. After starting hydrochlorothiazide treatment (2 mg\/kg\/body), the infant\u2019s urine production reduced (2.85 mL\/kg\/h); however, severe hypokalemia and alkalosis followed. Spironolactone, an aldosterone antagonist, were added, with good therapeutic response. Hydrochlorothiazide was administered to the uncle, and his daily fluid intake decreased to 3\u20134 L. Given the family history, Sanger sequencing for the AVPR2 variant was performed on the boys and the infant\u2019s mother. Analysis showed hemizygous likely pathogenic variant c.335G&gt;A p. (Cys112Tyr) in the 2 boys and heterozygous (carrier) status of the mother. Within the same family, we observed phenotypic heterogeneity: one child died at the age of two, another lived well into ten years without therapy, and a four month-old baby could have had a poor outcome without specific treatment. Conclusions: NDI is a rare and possibly fatal genetic disorder with heterogeneous manifestations. In families with a history of NDI, molecular genetic testing is crucial for family planning.<\/jats:p>","DOI":"10.3390\/children12020195","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T11:32:32Z","timestamp":1738841552000},"page":"195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nephrogenic Diabetes Insipidus Affecting Three Males in Two Generations\u2014Case Report and Review of the Literature"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-0581","authenticated-orcid":false,"given":"Ramona","family":"Stroescu","sequence":"first","affiliation":[{"name":"\u201cLouis Turcanu\u201d Children\u2019s Clinical and Emergency Hospital, Iosif Nemoianu 2, 300011 Timisoara, Romania"},{"name":"Department XI of Pediatrics, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7554-4625","authenticated-orcid":false,"given":"Adela","family":"Chiri\u0163\u0103-Emandi","sequence":"additional","affiliation":[{"name":"\u201cLouis Turcanu\u201d Children\u2019s Clinical and Emergency Hospital, Iosif Nemoianu 2, 300011 Timisoara, Romania"},{"name":"Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Puiu","sequence":"additional","affiliation":[{"name":"\u201cLouis Turcanu\u201d Children\u2019s Clinical and Emergency Hospital, Iosif Nemoianu 2, 300011 Timisoara, Romania"},{"name":"Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9456-4517","authenticated-orcid":false,"given":"Flavia","family":"Chisavu","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine \u201cVictor Babes\u201d, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruxandra","family":"Steflea","sequence":"additional","affiliation":[{"name":"\u201cLouis Turcanu\u201d Children\u2019s Clinical and Emergency Hospital, Iosif Nemoianu 2, 300011 Timisoara, Romania"},{"name":"Department XI of Pediatrics, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-4034","authenticated-orcid":false,"given":"Gabriela","family":"Doro\u015f","sequence":"additional","affiliation":[{"name":"\u201cLouis Turcanu\u201d Children\u2019s Clinical and Emergency Hospital, Iosif Nemoianu 2, 300011 Timisoara, Romania"},{"name":"Department XI of Pediatrics, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9029-5919","authenticated-orcid":false,"given":"Mihai","family":"Gafencu","sequence":"additional","affiliation":[{"name":"\u201cLouis Turcanu\u201d Children\u2019s Clinical and Emergency Hospital, Iosif Nemoianu 2, 300011 Timisoara, Romania"},{"name":"Department XI of Pediatrics, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1210\/er.2012-1044","article-title":"Nephrogenic Diabetes Insipidus: Essential Insights into the Molecular Background and Potential Therapies for Treatment","volume":"34","author":"Moeller","year":"2013","journal-title":"Endocr. 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