{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:35Z","timestamp":1784557055299,"version":"3.55.0"},"reference-count":20,"publisher":"Bioscientifica","license":[{"start":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T00:00:00Z","timestamp":1518134400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/deed.en_GB"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,2,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Activating mutations in\n                    <jats:italic>AVPR2<\/jats:italic>\n                    are associated with nephrogenic syndrome of inappropriate antidiuresis (NSIAD). NSIAD causes hyponatremia, decreased serum osmolality and clinical symptoms, which may present from birth or in infancy and include hypotonia, irritability, vomiting and\/or seizures. Symptoms in later life are often less specific and include malaise, dizziness, confusion, tiredness and headache. NSIAD is a rare X-linked condition, which is associated with a variable phenotype in males, of whom some present in infancy but others do not become symptomatic until adulthood, or occasionally, never. Female carriers may present with episodes of hyponatremia, usually found incidentally. Literature in this field is limited; namely, two clinical reports describing a female proband, both diagnosed in infancy. We describe, for the first time, the case of an adult female proband with NSIAD, who had longstanding associated symptoms of tiredness, headache, temporary memory loss and mood changes as well as hyponatremia and decreased serum osmolality. A water load test demonstrated an inability to dilute urine and gene sequencing confirmed a recurrent activating mutation in\n                    <jats:italic>AVPR2<\/jats:italic>\n                    . The variant was inherited from the proband\u2019s mother who had had longstanding episodes of transient asymptomatic hyponatremia. This is the third report of a female proband with NSIAD and is the first female reported who sought medical treatment for chronic symptoms from adulthood. This case acts as a reminder of the importance of considering NSIAD as a diagnosis in females of all ages with unexplained hyponatremia.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>Learning points:<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>\n                          Activating mutations in the\n                          <jats:italic>AVPR2<\/jats:italic>\n                          gene are associated with the rare X-linked condition nephrogenic syndrome of inappropriate antidiuresis.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>NSIAD is associated with hyponatremia, decreased serum osmolality and inappropriately increased urinary osmolality. Early clinical symptoms in infancy include hypotonia, irritability, vomiting and\/or seizures. Symptoms in later life include malaise, dizziness, confusion, tiredness and headache.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          NSIAD should be considered in female, as well as male, patients who present with unexplained hyponatremia and decreased serum osmolality. Family history may reveal relevant symptoms or biochemical features in other family members. However, family history may not always be informative due to the variable nature of the condition or if the proband has a\n                          <jats:italic>de novo<\/jats:italic>\n                          pathogenic variant.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>A water load test with measurement of AVP may be informative in distinguishing NSIAD from SIADH. Measurement of co-peptin levels may be considered, in substitution for direct measurement of AVP.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Patients with NSIAD should be counseled about appropriate daily fluid volume intake. Potential episodes of fluid overload should be avoided.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>","DOI":"10.1530\/edm-17-0139","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T05:45:34Z","timestamp":1518155134000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":3,"title":["Adult female with symptomatic AVPR2-related nephrogenic syndrome of inappropriate antidiuresis (NSIAD)"],"prefix":"10.1530","volume":"2018","author":[{"given":"Jennifer","family":"Hague","sequence":"first","affiliation":[{"name":"1Departments of Clinical GeneticsCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Casey","sequence":"additional","affiliation":[{"name":"2Departments of Diabetes and EndocrinologyCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"},{"name":"3Department of Medical GeneticsUniversity of Cambridge and NIHR Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Centre, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Bruty","sequence":"additional","affiliation":[{"name":"1Departments of Clinical GeneticsCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Legerton","sequence":"additional","affiliation":[{"name":"1Departments of Clinical GeneticsCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Abbs","sequence":"additional","affiliation":[{"name":"1Departments of Clinical GeneticsCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Oddy","sequence":"additional","affiliation":[{"name":"4Department of Clinical BiochemistryCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"Powlson","sequence":"additional","affiliation":[{"name":"2Departments of Diabetes and EndocrinologyCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Majeed","sequence":"additional","affiliation":[{"name":"2Departments of Diabetes and EndocrinologyCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gurnell","sequence":"additional","affiliation":[{"name":"2Departments of Diabetes and EndocrinologyCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Mi","family":"Park","sequence":"additional","affiliation":[{"name":"1Departments of Clinical GeneticsCambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Simpson","sequence":"additional","affiliation":[{"name":"5Department of Diabetes and EndocrinologyUCLH NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref31","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000381586","article-title":"Nephrogenic syndrome of inappropriate antidiuresis in a female neonate: review of the clinical presentation in females","volume":"84","year":"2015","journal-title":"Hormone Research in Paediatrics"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/ki.2015.181","article-title":"Mutation in the V2 vasopressin receptor gene, AVPR2, causes nephrogenic syndrome of inappropriate diuresis","volume":"88","year":"2015","journal-title":"Kidney International"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1056\/NEJMoa042743","article-title":"Nephrogenic syndrome of inappropriate antidiuresis","volume":"352","year":"2005","journal-title":"New England Journal of Medicine"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for molecular pathology","volume":"17","year":"2015","journal-title":"Genetics in Medicine"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1530\/EJE-09-0246","article-title":"Thirst perception and arginine vasopressin production in a kindred with an activating mutation of the type 2 vasopressin receptor: the pathophysiology of nephrogenic syndrome of inappropriate antidiuresis","volume":"161","year":"2009","journal-title":"European Journal of Endocrinology"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1056\/NEJMoa042743","article-title":"Nephrogenic syndrome of inappropriate antidiuresis","volume":"352","year":"2005","journal-title":"New England Journal of Medicine"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1530\/EJE-09-0246","article-title":"Thirst perception and arginine vasopressin production in a kindred with an activating mutation of the type 2 vasopressin receptor: the pathophysiology of nephrogenic syndrome of inappropriate antidiuresis","volume":"161","year":"2009","journal-title":"European Journal of Endocrinology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1053\/j.ajkd.2011.09.026","article-title":"A family with hyponatremia and the nephrogenic syndrome of inappropriate antidiuresis","volume":"59","year":"2012","journal-title":"American Journal of Kidney Diseases"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/cen.13011","article-title":"Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2","volume":"85","year":"2016","journal-title":"Clinical Endocrinology"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for molecular pathology","volume":"17","year":"2015","journal-title":"Genetics in Medicine"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/ki.2015.181","article-title":"Mutation in the V2 vasopressin receptor gene, AVPR2, causes nephrogenic syndrome of inappropriate diuresis","volume":"88","year":"2015","journal-title":"Kidney International"},{"key":"ref41","first-page":"37","article-title":"JamotMBlanchardGDubourgLHadj Familial nephrogenic syndrome of inappropriate antidiuresis : dissociation between aquaporin vasopressin excretion of and https org","author":"RanchinBBoury","journal-title":"Journal Clinical Endocrinology Metabolism"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/359233a0","article-title":"Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus","volume":"359","year":"1992","journal-title":"Nature"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1053\/j.ajkd.2011.09.026","article-title":"A family with hyponatremia and the nephrogenic syndrome of inappropriate antidiuresis","volume":"59","year":"2012","journal-title":"American Journal of Kidney Diseases"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1681\/ASN.2006090987","article-title":"Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic variability in men and women from a large pedigree","volume":"18","year":"2007","journal-title":"Journal of the American Society of Nephrology"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/cen.13011","article-title":"Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2","volume":"85","year":"2016","journal-title":"Clinical Endocrinology"},{"key":"ref141","first-page":"37","article-title":"JamotMBlanchardGDubourgLHadj Familial nephrogenic syndrome of inappropriate antidiuresis : dissociation between aquaporin vasopressin excretion of and https org","author":"RanchinBBoury","journal-title":"Journal Clinical Endocrinology Metabolism"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1681\/ASN.2006090987","article-title":"Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic variability in men and women from a large pedigree","volume":"18","year":"2007","journal-title":"Journal of the American Society of Nephrology"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/359233a0","article-title":"Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus","volume":"359","year":"1992","journal-title":"Nature"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000381586","article-title":"Nephrogenic syndrome of inappropriate antidiuresis in a female neonate: review of the clinical presentation in females","volume":"84","year":"2015","journal-title":"Hormone Research in Paediatrics"}],"container-title":["Endocrinology, Diabetes &amp; Metabolism Case Reports"],"original-title":[],"link":[{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2018\/1\/EDM17-0139.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2018\/1\/EDM17-0139.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:46:44Z","timestamp":1784555204000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/edm\/article\/3120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,9]]},"references-count":20,"URL":"https:\/\/doi.org\/10.1530\/edm-17-0139","relation":{},"ISSN":["2052-0573"],"issn-type":[{"value":"2052-0573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,9]]}}}