Case Report: A Multisystem Mystery: Unraveling HNF1β-Associated Glomerulocystic Disease in a 30-year-old Female

Case Report: A Multisystem Mystery: Unraveling HNF1β-Associated Glomerulocystic Disease in a 30-year-old Female | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Case Report: A Multisystem Mystery: Unraveling HNF1β-Associated Glomerulocystic Disease in a 30-year-old Female George Bonifant, Rabindra Dhakal, Oluwakorede Akele, Yisroel Grabie, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6551312/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The hepatocyte nuclear factor 1 beta (HNF1β) gene codes for a transcription factor involved in embryonic development and mitochondrial function, primarily in the kidney, liver, pancreas, and reproductive system. HNF1β-associated glomerular cystic kidney disease is a rare hereditary condition characterized by electrolyte disturbances, renal abnormalities, and multisystem involvement, commonly presenting as Renal Cysts and Diabetes (RCAD), often accompanied by maturity-onset diabetes of the young (MODY). We report a case of a 30-year-old female with no significant medical history who presented with severe abdominal pain radiating to her back, nausea, and vomiting. Initial evaluation revealed hypomagnesemia, hypokalemia, elevated liver function tests, renal and hepatic cysts, and a congenital bicornuate uterus. Genetic testing confirmed the diagnosis, identifying an HNF1β mutation due to a 17q12 deletion. She received symptomatic treatment, including pain management, electrolyte replacement, and supportive care. Attempts with amiloride and oral magnesium supplementation failed to maintain therapeutic magnesium levels, resulting in recurrent hospitalizations. Consequently, the patient required ongoing outpatient intravenous magnesium infusions (4 grams thrice weekly), effectively preventing further admissions. She also receives Vitamin D supplementation. Despite the typical disease association with MODY, she has no evidence of diabetes mellitus. This case highlights the complexity of HNF1β-associated glomerulocystic kidney disease, underscoring the importance of genetic testing for accurate diagnosis and treatment. It also emphasizes the necessity of a multidisciplinary management strategy to address this rare condition's diverse clinical manifestations and prevent recurrent complications. HNF1β-associated glomerulocystic kidney disease Genetic testing Electrolyte abnormalities Renal cysts Hypomagnesemia Figures Figure 1 Introduction Hepatocyte nuclear factor 1 beta (HNF1β)-associated glomerulocystic disease is a hereditary cystic kidney disease with a wide range of clinical manifestations, both renal and systemic. Hereditary cystic kidney diseases are caused by over 70 genes, which are generally inherited in an autosomal recessive manner. However, expression of the HNF1β gene leads to an autosomal dominant inheritance [ 1 ]. Clinical presentations include congenital renal anomalies, hypoplastic glomeruli, cystic kidney disease, cystic renal dysplasia, solitary functioning kidney, and oligomeganephronia [ 2 ]. HNF1β, located on chromosome 17q12, regulates gene expression and embryogenesis in the kidneys, liver, pancreas, and genital tract. HNF1β is essential for ureteric bud branching, initiation of nephrogenesis, and nephron segmentation in kidney development. Pathologic variants in HNF1β include deletions, truncations, and missense mutations that cause amino acid substitutions [ 3 ]. HNF1β mutations, initially identified in maturity-onset diabetes of the young type 5 (MODY5), frequently affect the kidneys, particularly in pediatric patients [ 4 ]. Approximately 30 heterozygous mutations have been identified, predominantly familial [ 5 ]. HNF1β mutations cause diverse renal phenotypes, accounting for 20–30% of fetuses with renal abnormalities and are the primary prenatal cause of hyperechogenic kidneys [ 5 , 6 ]. These mutations disrupt nephrogenesis and tubular orientation, leading to cyst formation [ 6 ]. They account for nearly 10% of unexplained renal diseases, indicating significant but underrecognized prevalence [ 5 ]. Renal manifestations include multi-cystic dysplastic kidneys, glomerulocystic kidney disease, autosomal dominant tubulointerstitial kidney disease, and polycystic kidney disease, potentially causing renal failure and hypertension. Extrarenal symptoms involve neurodevelopmental disorders, elevated liver enzymes, facial dysmorphisms, and urogenital anomalies [ 7 , 8 ]. Hypomagnesemia occurs in nearly half of affected patients due to reduced FXYD2 gene expression, which is regulated by HNF1β, and affects magnesium handling [ 9 ]. Hypokalemia frequently accompanies hypomagnesemia due to disrupted renal potassium handling influenced by HNF1β [ 10 ]. HNF1β mutations are associated with multiple cancers, including prostate, ovarian, and renal cancers [ 11 ]. Diagnosis can be challenging due to varied presentations and limited family history. An HNF1β score helps determine eligibility for genetic testing [ 12 ]. Management involves multidisciplinary symptomatic treatment, monitoring renal function, controlling diabetes and hypertension, and correcting electrolyte imbalances. Genetic testing is recommended for asymptomatic relatives [ 13 ]. Progression to end-stage kidney disease is rare. Case report A 30-year-old female with no significant past medical history presented to the emergency department with a chief complaint of severe abdominal pain radiating to her back. Episodes of nausea and non-bloody, non-bilious vomiting accompanied this. She mentioned that she had intermittent abdominal pain for the past 2–3 months, but in the past 2–3 days, the pain had been constant. The patient reported a decreased appetite for two days due to the pain. She denied fevers, chills, chest pain, shortness of breath, diarrhea, dysuria, hematuria, or vaginal bleeding. On exam, she appeared pale and dehydrated, with tenderness in the right upper quadrant of her abdomen. She also reported recently being evaluated for elevated liver function tests (LFTs) at another institution. She was afebrile and hemodynamically stable, with regular cardiovascular, respiratory, and musculoskeletal exams. She was found to have a magnesium level of 0.8 mg/dL and a potassium level of 3.3 mg/dL, with her liver function tests (LFTs) showing a total bilirubin of 2.9 mg/dL and a direct bilirubin of 0.5 mg/dL. Her renal function was normal. She then underwent a CT scan of the abdomen and pelvis with oral and IV contrast, along with an ultrasound of the right upper quadrant. Imaging revealed mild wall thickening with slight mucosal hyperenhancement of the distal and terminal ileum, suggesting enteritis. She was also noted to have a bicornuate uterus, and multiple bilateral renal cysts and hepatic cysts were incidentally found. Her hypomagnesemia and hypokalemia were corrected with magnesium sulfate and potassium chloride. In the ED, she received symptomatic treatment, including ondansetron, diphenhydramine, ketorolac, morphine, and pantoprazole, and was admitted for further evaluation and management. Surgery was consulted to rule out any acute pathology, including acute pancreatitis, acute cholecystitis, cholelithiasis, and acute appendicitis. Hepatology was consulted for the abnormal liver function tests (LFTs). The diagnostic assessment included considering differential diagnoses such as enteritis, biliary colic, Gilbert syndrome, or drug-induced liver injury. Nephrology was consulted for electrolyte abnormalities, attributing the hypomagnesemia and hypokalemia to decreased oral intake, vomiting, or a genetic condition. Gitelman syndrome was also considered, given her hypomagnesemia and borderline hypotension on presentation. Her symptoms improved with IV fluids, electrolyte repletion, and pain management. Although her LFTs normalized, her total bilirubin level remained elevated. She was discharged with prescriptions for magnesium oxide and dicyclomine. Discharge plans included outpatient follow-up with hepatology, where she underwent testing for celiac disease, Wilson's disease, and hepatitis B and C, all of which were negative. She was recommended to undergo an MRI of her kidneys, undergo genetic testing for HNF1β mutations, and have spot urine tests for magnesium, potassium, creatinine, and protein (Fig. 1 ). The patient again presented to the ED one week later with severe right upper quadrant pain that radiated to her back, initially intermittent but then became constant a week after discharge. She also presented with nausea and vomiting and was found to have a magnesium level of 1.5 mg/dL and a potassium level of 3.4 mg/dL. Her LFTs revealed an elevated total bilirubin of 1.6 mg/dL. She showed indirect bilirubinemia, supporting a diagnosis of Gilbert's syndrome. She presented with the same clinical and physical examination findings as the first visit. She then underwent a CT scan of the abdomen and pelvis with oral and IV contrast, which showed mild wall thickening of the distal and terminal ileum that had resolved compared to the prior CT scan. Acute pathologies were ruled out, and she was admitted for pain control and electrolyte management. She underwent an MRI of the abdomen with MRCP, which was normal except for the presence of hepatic cysts and bilateral tubular microcysts along the corticomedullary junction. Magnesuria was confirmed with a 24-hour magnesium collection test, which showed a level of 544 mg over 24 hours. Throughout the visit, she had hypomagnesemia and required continual correction. She was discharged with amiloride, with the rationale for using this medication based on the distal tubule handling of magnesium, which is partly influenced by overall intraluminal positivity and the concentration of sodium ions. By increasing the intraluminal sodium concentration, it is postulated that an increase in intraluminal ion positivity will enhance magnesium reabsorption, a mechanism often used to treat similar distal tubular disorders, such as Gitelman syndrome. Outpatient follow-up was scheduled with gastroenterology, where she underwent an upper endoscopy and a colonoscopy. The studies revealed diffuse erythema of the stomach mucosa, compatible with non-erosive gastritis. She also followed up with nephrology, where they suggested a genetic condition, such as HNF1β-associated disease, as the cause of her overall syndrome, which was later confirmed with genetic testing. Her condition is currently controlled with outpatient magnesium sulfate infusions thrice weekly, and she has been able to avoid further hospitalizations because of this infusion plan. Discussion This case contributes to the growing knowledge of HNF1β-associated glomerulocystic disease and highlights the importance of genetic testing for patients with unexplained renal and hepatic abnormalities. Early recognition of this condition can guide appropriate management strategies and genetic counseling. The treatment approach focused on symptomatic relief, electrolyte replacement, and a multidisciplinary evaluation to obtain a definitive diagnosis. This aligns with the conservative management strategies in the literature for chronic kidney disease, focusing on supportive care, symptomatic management, and regular monitoring. Previous literature has described pregnancy outcomes in women with maternal HNF1β gene mutations and 17q12 deletions, demonstrating a significant variability in clinical presentation and severity. Documented pregnancy complications in women with these mutations include polyhydramnios, preeclampsia, fetal macrosomia, preterm delivery, intrauterine fetal death, fetal growth restriction, and neonatal hyperinsulinemic hypoglycemia [ 14 ]. Maternal renal dysfunction, diabetes mellitus, and uterine anomalies are key contributors to adverse maternal and fetal outcomes [ 14 ]. The condition requires close surveillance during pregnancy, and genetic testing plays a crucial role in early identification and management, including pre-implantation genetic diagnosis, prenatal diagnostic gene testing, and careful postpartum monitoring due to the risks of ongoing renal, metabolic, and neurodevelopmental disorders [ 14 ]. By sharing this case, we aim to contribute to the existing literature on the diverse clinical manifestations of HNF1β mutations and highlight the need for a multidisciplinary approach to caring for affected individuals. Key lessons learned include the need for a thorough differential diagnosis to rule out other potential causes before considering a rare genetic condition. Genetic testing should be considered in patients with multiple unexplained renal cysts and associated electrolyte abnormalities. A multidisciplinary approach involving nephrology, hepatology, and genetics is crucial for comprehensive management. Recommendations for future practice in managing this condition include increasing awareness and early testing for genetic cystic kidney diseases in similar clinical scenarios, as well as continued research into the long-term outcomes and optimal management strategies for HNF1β-associated diseases. Declarations Conflict of interest: The authors have declared that no Conflict of interest exists. Informed consent: Informed consent was obtained from all individual participants included in the study. Ethical Approval: This case report was reviewed by the Institutional Review Board (IRB) of Staten Island University Hospital, which determined that formal IRB approval was not required and waived the need for ethics committee review in accordance with institutional policy and the U.S. Department of Health and Human Services regulations at 45 CFR 46.102. The case was conducted in accordance with the ethical standards and guidelines of the IRB. Written informed consent was obtained from the patient for publication of all clinical information and accompanying images. Data availability statement: Data supporting the findings of this study are available within the article. Further information is available from the corresponding author on reasonable request. Funding statement: The author received no financial support for the research, authorship, and/or publication of this article. Clinical Trial Number: not applicable. Consent to Participate: Informed consent was obtained from all individual participants included in the study. Consent to Publish: The patient gave written informed consent to the publication of the clinical details and clinical images in this manuscript. References Goknar N, Ekici Avci M, Uckardes D, Kelesoglu E, Tekkus Ermis K, Candan C. Hepatocyte Nuclear Factor 1 Beta Mutation-associated Newborn Onset of Glomerulocystic Kidney Disease: A Case Presentation. Medeni Med J . 2021;36(4):352–355. doi: 10.4274/MMJ.galenos.2021.02686 Bingham C, Ellard S, van't Hoff WG, et al. Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation. Kidney Int . 2003;63(5):1645–1651. doi: 10.1046/j.1523-1755.2003.00903.x Bleyer AJ, Kmoch S. The Varied Clinical Presentation of Autosomal Dominant Tubulointerstitial Kidney Disease Due to HNF1β Mutations. Kidney Int Rep. 2020;5(12):2133–2135. doi: 10.1016/j.ekir.2020.10.008 . PMID: 33306044; PMCID: PMC7710887. Alvelos MI, Rodrigues M, Lobo L, et al. A novel mutation of the HNF1β gene associated with hypoplastic glomerulocystic kidney disease and neonatal renal failure: a case report and mutation update. Medicine (Baltimore) . 2015;94(7):e469. doi: 10.1097/MD.0000000000000469 Edghill EL, Bingham C, Ellard S, Hattersley AT. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet . 2006;43(1):84–90. doi: 10.1136/jmg.2005.032854 Ferrè S, Igarashi P. New insights into the role of HNF-1β in kidney (patho)physiology. Pediatr Nephrol . 2019;34(8):1325–1335. doi: 10.1007/s00467-018-3990-7 Shao A, Chan SC, Igarashi P. Role of transcription factor hepatocyte nuclear factor-1β in polycystic kidney disease. Cell Signal . 2020;71:109568. doi: 10.1016/j.cellsig.2020.109568 Alvelos MI, Rodrigues M, Lobo L, et al. A novel mutation of the HNF1β gene associated with hypoplastic glomerulocystic kidney disease and neonatal renal failure: a case report and mutation update. Medicine (Baltimore) . 2015;94(7):e469. doi: 10.1097/MD.0000000000000469 Gambella A, Kalantari S, Cadamuro M, Quaglia M, Delvecchio M, Fabris L, Pinon M. The Landscape of HNF1B Deficiency: A Syndrome Not Yet Fully Explored. Cells. 2023;12(2):307. doi: 10.3390/cells12020307 . PMID: 36672242; PMCID: PMC9856658. Ferrè S, Igarashi P. New insights into the role of HNF-1β in kidney (patho)physiology. Pediatr Nephrol . 2019;34(8):1325–1335. doi: 10.1007/s00467-018-3990-7 Chandra S, Srinivasan S, Batra J. Hepatocyte nuclear factor 1 beta: A perspective in cancer. Cancer Med . 2021;10(5):1791–1804. doi: 10.1002/cam4.3676 Clissold R, Shields B, Ellard S, Hattersley A, Bingham C. Assessment of the HNF1β Score as a Tool to Select Patients for HNF1β Genetic Testing. Nephron . 2015;130(2):134–140. doi: 10.1159/000398819 Salazar L, Sousa B, Ventura S, et al. #5283 HNF1β MUTATIONS AND ASSOCIATED PHENOTYPES – WHAT TO LOOK FOR? Nephrology, dialysis, transplantation/Nephrology dialysis transplantation . 2023;38(Supplement_1). doi: https://doi.org/10.1093/ndt/gfad063c_5283 Morton A, Li L, Wilson C. Pregnancy outcome with maternal HNF1B gene mutations and 17q12 deletions. Obstet Med . 2023;16(2):78–82. doi: 10.1177/1753495X221109734 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6551312","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":469363895,"identity":"97fbd62f-3cc2-4dd3-8a8d-c84270d99a75","order_by":0,"name":"George Bonifant","email":"","orcid":"","institution":"Northwell Health","correspondingAuthor":false,"prefix":"","firstName":"George","middleName":"","lastName":"Bonifant","suffix":""},{"id":469363896,"identity":"76700771-2c02-4c42-a0ee-c67386e3a2c9","order_by":1,"name":"Rabindra Dhakal","email":"","orcid":"","institution":"Northwell Health","correspondingAuthor":false,"prefix":"","firstName":"Rabindra","middleName":"","lastName":"Dhakal","suffix":""},{"id":469363897,"identity":"300e848c-12c9-495a-bf7b-bd9c16f17d33","order_by":2,"name":"Oluwakorede Akele","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYFACNgaGBww2UBaDhQyQMCCsJYEhDchgBmmR4CFWy2EStPCzH0t8kFBxPo9f+vyxxzwVQC3szdsk8GmR7Ek7bJBw5naxZF8yuzHPGaAWnmNleLUYHEhvk0hsu5244Qwzm3RuG1CLRI4Zfi3nn7f/SPx3DqrlH1CL/BsCWm6kHWNIbDgA1dIAsoUHvxbJGc+SJRKOJSfO7GE2k/5zTIKHjSet2AKfFn7+NMMPH2rsEvt5GJ9JzqixkeNnP7zxBj4tmICNNOWjYBSMglEwCrABAMPoQFzl6gYnAAAAAElFTkSuQmCC","orcid":"","institution":"Northwell Health","correspondingAuthor":true,"prefix":"","firstName":"Oluwakorede","middleName":"","lastName":"Akele","suffix":""},{"id":469363900,"identity":"4aa18e15-31f1-4acd-8423-4fbea8bfd6dd","order_by":3,"name":"Yisroel Grabie","email":"","orcid":"","institution":"Northwell Health","correspondingAuthor":false,"prefix":"","firstName":"Yisroel","middleName":"","lastName":"Grabie","suffix":""},{"id":469363902,"identity":"222e7fc6-d3a4-4e2e-bed7-6274045b7c30","order_by":4,"name":"Umesh Manchandani","email":"","orcid":"","institution":"Northwell Health","correspondingAuthor":false,"prefix":"","firstName":"Umesh","middleName":"","lastName":"Manchandani","suffix":""}],"badges":[],"createdAt":"2025-04-29 01:08:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6551312/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6551312/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84547628,"identity":"9e5eb724-71d4-4f18-8701-786c70ff28e4","added_by":"auto","created_at":"2025-06-13 09:28:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":353880,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A):\u003c/strong\u003e Coronal MRI of the abdomen with IV contrast, showing bilateral renal cysts and tubular microcysts located along the corticomedullary junction. \u003cstrong\u003e(B): \u003c/strong\u003eAxial MRI of the abdomen with IV contrast, highlighting the presence of tubular microcysts in the kidneys, consistent with HNF1β-associated glomerulocystic kidney disease.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6551312/v1/5dc8a8fff228faf1acac1515.png"},{"id":89278669,"identity":"f66383a5-2d02-4cb6-9604-ee8bb4a18803","added_by":"auto","created_at":"2025-08-18 10:02:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":837479,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6551312/v1/c275cfa6-8b05-4b87-95e3-8d1f0e44e617.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Case Report: A Multisystem Mystery: Unraveling HNF1β-Associated Glomerulocystic Disease in a 30-year-old Female","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatocyte nuclear factor 1 beta (HNF1β)-associated glomerulocystic disease is a hereditary cystic kidney disease with a wide range of clinical manifestations, both renal and systemic. Hereditary cystic kidney diseases are caused by over 70 genes, which are generally inherited in an autosomal recessive manner. However, expression of the HNF1β gene leads to an autosomal dominant inheritance [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Clinical presentations include congenital renal anomalies, hypoplastic glomeruli, cystic kidney disease, cystic renal dysplasia, solitary functioning kidney, and oligomeganephronia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHNF1β, located on chromosome 17q12, regulates gene expression and embryogenesis in the kidneys, liver, pancreas, and genital tract. HNF1β is essential for ureteric bud branching, initiation of nephrogenesis, and nephron segmentation in kidney development. Pathologic variants in HNF1β include deletions, truncations, and missense mutations that cause amino acid substitutions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. HNF1β mutations, initially identified in maturity-onset diabetes of the young type 5 (MODY5), frequently affect the kidneys, particularly in pediatric patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Approximately 30 heterozygous mutations have been identified, predominantly familial [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHNF1β mutations cause diverse renal phenotypes, accounting for 20\u0026ndash;30% of fetuses with renal abnormalities and are the primary prenatal cause of hyperechogenic kidneys [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These mutations disrupt nephrogenesis and tubular orientation, leading to cyst formation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. They account for nearly 10% of unexplained renal diseases, indicating significant but underrecognized prevalence [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Renal manifestations include multi-cystic dysplastic kidneys, glomerulocystic kidney disease, autosomal dominant tubulointerstitial kidney disease, and polycystic kidney disease, potentially causing renal failure and hypertension. Extrarenal symptoms involve neurodevelopmental disorders, elevated liver enzymes, facial dysmorphisms, and urogenital anomalies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHypomagnesemia occurs in nearly half of affected patients due to reduced FXYD2 gene expression, which is regulated by HNF1β, and affects magnesium handling [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Hypokalemia frequently accompanies hypomagnesemia due to disrupted renal potassium handling influenced by HNF1β [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. HNF1β mutations are associated with multiple cancers, including prostate, ovarian, and renal cancers [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDiagnosis can be challenging due to varied presentations and limited family history. An HNF1β score helps determine eligibility for genetic testing [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Management involves multidisciplinary symptomatic treatment, monitoring renal function, controlling diabetes and hypertension, and correcting electrolyte imbalances. Genetic testing is recommended for asymptomatic relatives [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Progression to end-stage kidney disease is rare.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 30-year-old female with no significant past medical history presented to the emergency department with a chief complaint of severe abdominal pain radiating to her back. Episodes of nausea and non-bloody, non-bilious vomiting accompanied this. She mentioned that she had intermittent abdominal pain for the past 2\u0026ndash;3 months, but in the past 2\u0026ndash;3 days, the pain had been constant. The patient reported a decreased appetite for two days due to the pain. She denied fevers, chills, chest pain, shortness of breath, diarrhea, dysuria, hematuria, or vaginal bleeding. On exam, she appeared pale and dehydrated, with tenderness in the right upper quadrant of her abdomen. She also reported recently being evaluated for elevated liver function tests (LFTs) at another institution. She was afebrile and hemodynamically stable, with regular cardiovascular, respiratory, and musculoskeletal exams.\u003c/p\u003e \u003cp\u003eShe was found to have a magnesium level of 0.8 mg/dL and a potassium level of 3.3 mg/dL, with her liver function tests (LFTs) showing a total bilirubin of 2.9 mg/dL and a direct bilirubin of 0.5 mg/dL. Her renal function was normal. She then underwent a CT scan of the abdomen and pelvis with oral and IV contrast, along with an ultrasound of the right upper quadrant. Imaging revealed mild wall thickening with slight mucosal hyperenhancement of the distal and terminal ileum, suggesting enteritis. She was also noted to have a bicornuate uterus, and multiple bilateral renal cysts and hepatic cysts were incidentally found. Her hypomagnesemia and hypokalemia were corrected with magnesium sulfate and potassium chloride. In the ED, she received symptomatic treatment, including ondansetron, diphenhydramine, ketorolac, morphine, and pantoprazole, and was admitted for further evaluation and management.\u003c/p\u003e \u003cp\u003eSurgery was consulted to rule out any acute pathology, including acute pancreatitis, acute cholecystitis, cholelithiasis, and acute appendicitis. Hepatology was consulted for the abnormal liver function tests (LFTs). The diagnostic assessment included considering differential diagnoses such as enteritis, biliary colic, Gilbert syndrome, or drug-induced liver injury. Nephrology was consulted for electrolyte abnormalities, attributing the hypomagnesemia and hypokalemia to decreased oral intake, vomiting, or a genetic condition. Gitelman syndrome was also considered, given her hypomagnesemia and borderline hypotension on presentation. Her symptoms improved with IV fluids, electrolyte repletion, and pain management. Although her LFTs normalized, her total bilirubin level remained elevated. She was discharged with prescriptions for magnesium oxide and dicyclomine. Discharge plans included outpatient follow-up with hepatology, where she underwent testing for celiac disease, Wilson's disease, and hepatitis B and C, all of which were negative. She was recommended to undergo an MRI of her kidneys, undergo genetic testing for HNF1β mutations, and have spot urine tests for magnesium, potassium, creatinine, and protein (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient again presented to the ED one week later with severe right upper quadrant pain that radiated to her back, initially intermittent but then became constant a week after discharge. She also presented with nausea and vomiting and was found to have a magnesium level of 1.5 mg/dL and a potassium level of 3.4 mg/dL. Her LFTs revealed an elevated total bilirubin of 1.6 mg/dL. She showed indirect bilirubinemia, supporting a diagnosis of Gilbert's syndrome. She presented with the same clinical and physical examination findings as the first visit. She then underwent a CT scan of the abdomen and pelvis with oral and IV contrast, which showed mild wall thickening of the distal and terminal ileum that had resolved compared to the prior CT scan. Acute pathologies were ruled out, and she was admitted for pain control and electrolyte management. She underwent an MRI of the abdomen with MRCP, which was normal except for the presence of hepatic cysts and bilateral tubular microcysts along the corticomedullary junction. Magnesuria was confirmed with a 24-hour magnesium collection test, which showed a level of 544 mg over 24 hours. Throughout the visit, she had hypomagnesemia and required continual correction.\u003c/p\u003e \u003cp\u003eShe was discharged with amiloride, with the rationale for using this medication based on the distal tubule handling of magnesium, which is partly influenced by overall intraluminal positivity and the concentration of sodium ions. By increasing the intraluminal sodium concentration, it is postulated that an increase in intraluminal ion positivity will enhance magnesium reabsorption, a mechanism often used to treat similar distal tubular disorders, such as Gitelman syndrome. Outpatient follow-up was scheduled with gastroenterology, where she underwent an upper endoscopy and a colonoscopy. The studies revealed diffuse erythema of the stomach mucosa, compatible with non-erosive gastritis. She also followed up with nephrology, where they suggested a genetic condition, such as HNF1β-associated disease, as the cause of her overall syndrome, which was later confirmed with genetic testing. Her condition is currently controlled with outpatient magnesium sulfate infusions thrice weekly, and she has been able to avoid further hospitalizations because of this infusion plan.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case contributes to the growing knowledge of HNF1β-associated glomerulocystic disease and highlights the importance of genetic testing for patients with unexplained renal and hepatic abnormalities. Early recognition of this condition can guide appropriate management strategies and genetic counseling. The treatment approach focused on symptomatic relief, electrolyte replacement, and a multidisciplinary evaluation to obtain a definitive diagnosis. This aligns with the conservative management strategies in the literature for chronic kidney disease, focusing on supportive care, symptomatic management, and regular monitoring.\u003c/p\u003e \u003cp\u003ePrevious literature has described pregnancy outcomes in women with maternal HNF1β gene mutations and 17q12 deletions, demonstrating a significant variability in clinical presentation and severity. Documented pregnancy complications in women with these mutations include polyhydramnios, preeclampsia, fetal macrosomia, preterm delivery, intrauterine fetal death, fetal growth restriction, and neonatal hyperinsulinemic hypoglycemia [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Maternal renal dysfunction, diabetes mellitus, and uterine anomalies are key contributors to adverse maternal and fetal outcomes [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The condition requires close surveillance during pregnancy, and genetic testing plays a crucial role in early identification and management, including pre-implantation genetic diagnosis, prenatal diagnostic gene testing, and careful postpartum monitoring due to the risks of ongoing renal, metabolic, and neurodevelopmental disorders [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBy sharing this case, we aim to contribute to the existing literature on the diverse clinical manifestations of HNF1β mutations and highlight the need for a multidisciplinary approach to caring for affected individuals. Key lessons learned include the need for a thorough differential diagnosis to rule out other potential causes before considering a rare genetic condition. Genetic testing should be considered in patients with multiple unexplained renal cysts and associated electrolyte abnormalities. A multidisciplinary approach involving nephrology, hepatology, and genetics is crucial for comprehensive management. Recommendations for future practice in managing this condition include increasing awareness and early testing for genetic cystic kidney diseases in similar clinical scenarios, as well as continued research into the long-term outcomes and optimal management strategies for HNF1β-associated diseases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have declared that no Conflict of interest exists.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report was reviewed by the Institutional Review Board (IRB) of Staten Island University Hospital, which determined that formal IRB approval was not required and waived the need for ethics committee review in accordance with institutional policy and the U.S. Department of Health and Human Services regulations at 45 CFR 46.102. The case was conducted in accordance with the ethical standards and guidelines of the IRB. Written informed consent was obtained from the patient for publication of all clinical information and accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData supporting the findings of this study are available within the article. Further information is available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number:\u003c/strong\u003e not applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate:\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish:\u003c/strong\u003e The patient gave written informed consent to the publication of the clinical details and clinical images in this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGoknar N, Ekici Avci M, Uckardes D, Kelesoglu E, Tekkus Ermis K, Candan C. Hepatocyte Nuclear Factor 1 Beta Mutation-associated Newborn Onset of Glomerulocystic Kidney Disease: A Case Presentation. \u003cem\u003eMedeni Med J\u003c/em\u003e. 2021;36(4):352\u0026ndash;355. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4274/MMJ.galenos.2021.02686\u003c/span\u003e\u003cspan address=\"10.4274/MMJ.galenos.2021.02686\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBingham C, Ellard S, van't Hoff WG, et al. Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation. \u003cem\u003eKidney Int\u003c/em\u003e. 2003;63(5):1645\u0026ndash;1651. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1046/j.1523-1755.2003.00903.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1523-1755.2003.00903.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBleyer AJ, Kmoch S. The Varied Clinical Presentation of Autosomal Dominant Tubulointerstitial Kidney Disease Due to \u003cem\u003eHNF1β\u003c/em\u003e Mutations. Kidney Int Rep. 2020;5(12):2133\u0026ndash;2135. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ekir.2020.10.008\u003c/span\u003e\u003cspan address=\"10.1016/j.ekir.2020.10.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 33306044; PMCID: PMC7710887.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlvelos MI, Rodrigues M, Lobo L, et al. A novel mutation of the HNF1β gene associated with hypoplastic glomerulocystic kidney disease and neonatal renal failure: a case report and mutation update. \u003cem\u003eMedicine (Baltimore)\u003c/em\u003e. 2015;94(7):e469. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000000469\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000000469\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEdghill EL, Bingham C, Ellard S, Hattersley AT. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. \u003cem\u003eJ Med Genet\u003c/em\u003e. 2006;43(1):84\u0026ndash;90. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/jmg.2005.032854\u003c/span\u003e\u003cspan address=\"10.1136/jmg.2005.032854\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerr\u0026egrave; S, Igarashi P. New insights into the role of HNF-1β in kidney (patho)physiology. \u003cem\u003ePediatr Nephrol\u003c/em\u003e. 2019;34(8):1325\u0026ndash;1335. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00467-018-3990-7\u003c/span\u003e\u003cspan address=\"10.1007/s00467-018-3990-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShao A, Chan SC, Igarashi P. Role of transcription factor hepatocyte nuclear factor-1β in polycystic kidney disease. \u003cem\u003eCell Signal\u003c/em\u003e. 2020;71:109568. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cellsig.2020.109568\u003c/span\u003e\u003cspan address=\"10.1016/j.cellsig.2020.109568\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlvelos MI, Rodrigues M, Lobo L, et al. A novel mutation of the HNF1β gene associated with hypoplastic glomerulocystic kidney disease and neonatal renal failure: a case report and mutation update. \u003cem\u003eMedicine (Baltimore)\u003c/em\u003e. 2015;94(7):e469. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000000469\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000000469\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGambella A, Kalantari S, Cadamuro M, Quaglia M, Delvecchio M, Fabris L, Pinon M. The Landscape of HNF1B Deficiency: A Syndrome Not Yet Fully Explored. Cells. 2023;12(2):307. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cells12020307\u003c/span\u003e\u003cspan address=\"10.3390/cells12020307\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 36672242; PMCID: PMC9856658.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerr\u0026egrave; S, Igarashi P. New insights into the role of HNF-1β in kidney (patho)physiology. \u003cem\u003ePediatr Nephrol\u003c/em\u003e. 2019;34(8):1325\u0026ndash;1335. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00467-018-3990-7\u003c/span\u003e\u003cspan address=\"10.1007/s00467-018-3990-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChandra S, Srinivasan S, Batra J. Hepatocyte nuclear factor 1 beta: A perspective in cancer. \u003cem\u003eCancer Med\u003c/em\u003e. 2021;10(5):1791\u0026ndash;1804. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/cam4.3676\u003c/span\u003e\u003cspan address=\"10.1002/cam4.3676\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClissold R, Shields B, Ellard S, Hattersley A, Bingham C. Assessment of the HNF1β Score as a Tool to Select Patients for HNF1β Genetic Testing. \u003cem\u003eNephron\u003c/em\u003e. 2015;130(2):134\u0026ndash;140. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000398819\u003c/span\u003e\u003cspan address=\"10.1159/000398819\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalazar L, Sousa B, Ventura S, et al. #5283 HNF1β MUTATIONS AND ASSOCIATED PHENOTYPES \u0026ndash; WHAT TO LOOK FOR? \u003cem\u003eNephrology, dialysis, transplantation/Nephrology dialysis transplantation\u003c/em\u003e. 2023;38(Supplement_1). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/ndt/gfad063c_5283\u003c/span\u003e\u003cspan address=\"10.1093/ndt/gfad063c_5283\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorton A, Li L, Wilson C. Pregnancy outcome with maternal \u003cem\u003eHNF1B\u003c/em\u003e gene mutations and 17q12 deletions. \u003cem\u003eObstet Med\u003c/em\u003e. 2023;16(2):78\u0026ndash;82. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1753495X221109734\u003c/span\u003e\u003cspan address=\"10.1177/1753495X221109734\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"HNF1β-associated glomerulocystic kidney disease, Genetic testing, Electrolyte abnormalities, Renal cysts, Hypomagnesemia","lastPublishedDoi":"10.21203/rs.3.rs-6551312/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6551312/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe hepatocyte nuclear factor 1 beta (HNF1β) gene codes for a transcription factor involved in embryonic development and mitochondrial function, primarily in the kidney, liver, pancreas, and reproductive system. HNF1β-associated glomerular cystic kidney disease is a rare hereditary condition characterized by electrolyte disturbances, renal abnormalities, and multisystem involvement, commonly presenting as Renal Cysts and Diabetes (RCAD), often accompanied by maturity-onset diabetes of the young (MODY). We report a case of a 30-year-old female with no significant medical history who presented with severe abdominal pain radiating to her back, nausea, and vomiting. Initial evaluation revealed hypomagnesemia, hypokalemia, elevated liver function tests, renal and hepatic cysts, and a congenital bicornuate uterus. Genetic testing confirmed the diagnosis, identifying an HNF1β mutation due to a 17q12 deletion. She received symptomatic treatment, including pain management, electrolyte replacement, and supportive care. Attempts with amiloride and oral magnesium supplementation failed to maintain therapeutic magnesium levels, resulting in recurrent hospitalizations. Consequently, the patient required ongoing outpatient intravenous magnesium infusions (4 grams thrice weekly), effectively preventing further admissions. She also receives Vitamin D supplementation. Despite the typical disease association with MODY, she has no evidence of diabetes mellitus. This case highlights the complexity of HNF1β-associated glomerulocystic kidney disease, underscoring the importance of genetic testing for accurate diagnosis and treatment. It also emphasizes the necessity of a multidisciplinary management strategy to address this rare condition's diverse clinical manifestations and prevent recurrent complications.\u003c/p\u003e","manuscriptTitle":"Case Report: A Multisystem Mystery: Unraveling HNF1β-Associated Glomerulocystic Disease in a 30-year-old Female","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-13 09:20:53","doi":"10.21203/rs.3.rs-6551312/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a4d12bb9-0716-4c96-884c-4875870e0585","owner":[],"postedDate":"June 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-18T09:54:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-13 09:20:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6551312","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6551312","identity":"rs-6551312","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}