{"doi":"10.1016/j.aace.2023.06.003","title":"Cystic and Atrophic Kidneys, Atrophic Pancreas, Arcuate Uterus, and Diabetes Mellitus Associated With Deletion of HNF1β Gene","abstract":"The patient is a 33-year-old female with end-stage kidney disease (ESKD) who was referred for diabetes management. She developed diabetes at age 30, 3 years prior to the referral, presenting with an A1c of 9.1%, BMI of 31 kg/m2. Notably, glucoses were normal for 4-5 years after her kidney transplant at age 25, increasing moderately in the year prior to referral. Diabetes testing revealed negative anti-GAD65 and anti-pancreatic islet cell antibodies. C-peptide was 2.9 ng/mL fasting and 5.2 ng/mL on a random check. She denied any family history of diabetes or renal disease. Glucose control improved rapidly with diet, exercise, GLP-1 agonist, and low doses of insulin. The patient’s kidney disease history includes progressive loss of kidney function as an adolescent and young adult with pre-transplant imaging at age 25 showing bilateral renal cysts and markedly atrophic left kidney (Figure 1). Imaging at age 31 showed scarred native kidneys and atrophy of the body and tail of the pancreas. Pelvic ultrasound showed an arcuate fundal uterine contour (Figure 2). What is the diagnosis?Figure 2Uterine abnormality. (A) Sketched coronal view of the uterus with a normal fundal contour. (B) Transvaginal ultrasound of the patient at a transverse plane below the arcuate contour. This image looks similar to imaging of a normal uterus at the transverse plane approximated in panel A (line). (C) Sketched coronal view of the uterus with an arcuate fundal contour (arrow). (D) Transvaginal ultrasound at the transverse plane approximated in panel C (line). The endometrial stripe is interrupted by the arcuate contour of the fundus (arrow).View Large Image Figure ViewerDownload Hi-res image Download (PPT) HNF1β-associated disease, also known as maturity onset diabetes of the young (MODY) type 5 and Renal Cysts and Diabetes Syndrome (RCAD). Genetic testing revealed complete deletion of the entire coding sequence of gene HNF1β. HNF1β -associated disease has variable penetrance and unknown prevalence. De novo mutations account for approximately 50% of cases, and phenotypic presentation is variable.1Faguer S. Decramer S. Chassaing N. et al.Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood.Kidney Int. 2011; 80: 768-776Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar Common clinical findings include congenital kidney disease with hyperechoic and/or cystic kidneys, onset of diabetes mellitus in adolescence or young adulthood with pancreatic hypoplasia or atrophy, genital tract malformations, abnormal liver function tests, hypomagnesemia, hyperuricemia and early onset gout. Secondary hyperparathyroidism, and neurologic features have also been described.2Clissold R.L. Hamilton A.J. Hattersley A.T. Ellard S. Bingham C. HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum.Nat Rev Nephrol. 2015; 11: 102-112Crossref PubMed Scopus (196) Google Scholar HNF1β is predominantly expressed in the kidneys and likely plays a role in tubular development. It also has an important role in urogenital and pancreas development.2Clissold R.L. Hamilton A.J. Hattersley A.T. Ellard S. Bingham C. HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum.Nat Rev Nephrol. 2015; 11: 102-112Crossref PubMed Scopus (196) Google Scholar This case highlights the importance of suspecting MODY, and specifically HNF1β defects, when patients present with this constellation of findings.3Broome D.T. Pantalone K.M. Kashyap S.R. Philipson L.H. Approach to the Patient with MODY-Monogenic Diabetes.J Clin Endocrinol Metab. 2021; 106: 237-250Crossref PubMed Scopus (44) Google Scholar Diagnostic workup includes antibody and C-peptide testing followed by molecular genetic testing. Establishing a MODY diagnosis is important as therapeutic strategies, transplant counseling, and routine health maintenance screenings vary by genetic mutation and mechanism of disease. Inheritance is generally autosomal dominant, which is impor","journal":"AACE Clinical Case Reports","year":2023,"id":388758,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":310794,"name":"Alberto Sobrero","orcid":"0000-0001-7764-673X","position":1,"is_corresponding":false},{"id":329348,"name":"Amy E. Riek","orcid":"0000-0003-4639-1281","position":2,"is_corresponding":false},{"id":231206,"name":"Janet B. McGill","orcid":"0000-0002-6228-6521","position":3,"is_corresponding":false},{"id":250010,"name":"Fumihiko Urano","orcid":"0000-0002-9944-6293","position":4,"is_corresponding":false},{"id":1158251,"name":"Rachel L. Usala","orcid":"0000-0002-3480-5996","position":0,"is_corresponding":true}],"reference_count":3,"raw_metadata":null,"created_at":"2026-07-19T01:18:18.214733Z","pmid":"38523851","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}