HNF1B-MODY Masquerading as Type 1 Diabetes: A Pitfall in the Etiological Diagnosis of Diabetes

Francis, Youmna; Tiercelin, Claudine; Alexandre-Heyman, Laure; Larger, Étienne; Dubois‐Laforgue, Danièle

doi:10.1210/jendso/bvac087

Cited by 7 publications

(4 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HNF1β is a TF that regulates the development and function of the pancreas, kidney, liver, and genital tract (47). Mutations in HNF1B lead to a variable clinical presentation, including diabetes, renal cysts and malformations, genital tract abnormalities, liver dysfunction, and pancreatic hypoplasia (Fig.…”

Section: Hnf1b-mody (Mody5)mentioning

confidence: 99%

Pancreatic Diseases: Genetics and Modeling Using Human Pluripotent Stem Cells

Lee,

Lee

2024

Int J Stem Cells

View full text Add to dashboard Cite

Pancreas serves endocrine and exocrine functions in the body; thus, their pathology can cause a broad range of irreparable consequences. Endocrine functions include the production of hormones such as insulin and glucagon, while exocrine functions involve the secretion of digestive enzymes. Disruption of these functions can lead to conditions like diabetes mellitus and exocrine pancreatic insufficiency. Also, the symptoms and causality of pancreatic cancer very greatly depends on their origin: pancreatic ductal adenocarcinoma is one of the most fatal cancer; however, most of tumor derived from endocrine part of pancreas are benign. Pancreatitis, an inflammation of the pancreatic tissues, is caused by excessive alcohol consumption, the bile duct obstruction by gallstones, and the premature activation of digestive enzymes in the pancreas. Hereditary pancreatic diseases, such as maturity-onset diabetes of the young and hereditary pancreatitis, can be a candidate for disease modeling using human pluripotent stem cells (hPSCs), due to their strong genetic influence. hPSC-derived pancreatic differentiation has been established for cell replacement therapy for diabetic patients and is robustly used for disease modeling. The disease modeling platform that allows interactions between immune cells and pancreatic cells is necessary to perform in-depth investigation of disease pathogenesis.

show abstract

Section: Hnf1b-mody (Mody5)mentioning

confidence: 99%

Pancreatic Diseases: Genetics and Modeling Using Human Pluripotent Stem Cells

Lee,

Lee

2024

Int J Stem Cells

View full text Add to dashboard Cite

show abstract

“…4 Pancreatic exocrine dysfunction and diabetes mellitus is described in 20%-75% of patients. 5 Diabetes usually presents after age 25 and often in lean patients. It may be erroneously labelled as type 1 diabetes.…”

Section: Hnf1b-modymentioning

confidence: 99%

“…It may be erroneously labelled as type 1 diabetes. 5 The absence of autoantibodies and residual insulin secretion evidenced by intact C-Peptide levels should point to the possibility of a monogenic condition. HNF1B accounts for 5% of MODY cases, and unlike other subtypes it does not respond well to sulfonylurea use and may require insulin.…”

Section: Hnf1b-modymentioning

confidence: 99%

Persistent hypomagnesaemia caused by HNF1B-MODY in a patient on platinum-based chemotherapy: A case report and review

Hayes,

Holian

2024

Journal of Onco-Nephrology

View full text Add to dashboard Cite

We report a case of a 60 year-old female with persistent refractory hypomagnaesemia caused by HNF1B gene deletion. Her hypomagnaesemia had been attributed to the use of adjuvant platinum chemotherapy administered 2 years previously following a haemicolectomy for colorectal cancer. However it emerged that she had HNF1B gene deletion and had been diagnosed with MODY thirteen years previously. Her hypomagnaesemia was in fact longstanding and predated chemotherapy use. Previous abdominal imaging showed bilateral renal cysts and uterine didelphys which are consistent with anatomical features of HNF1B dysfunction. Her hypomagnaesemia is most likely related to HNF1-MODY. She continues to be managed with regular magnesium infusions and will likely require this as a lifelong measure. This case served as a reminder to look beyond medications as a potential cause for hypomagnesaemia and consider rare genetic conditions.

show abstract

“…On this basis, it is not surprising that the liver phenotype of patients with HNF1B deficiency shows a cholestatic profile [15,[60][61][62][63]85,86], especially in the neonatal age. From a histopathological perspective, all the cholestatic patients reported above [60][61][62][63] had comparable histological features, showing a pattern of paucity of interlobular bile ducts (PILBD), associated with marked cholestasis and variable degrees of periportal fibrosis.…”

Section: Histopathology Of Non-neoplastic Conditionsmentioning

confidence: 99%

The Landscape of HNF1B Deficiency: A Syndrome Not Yet Fully Explored

Gambella

Kalantari

Cadamuro

et al. 2023

Cells

View full text Add to dashboard Cite

The hepatocyte nuclear factor 1β (HNF1B) gene is involved in the development of specialized epithelia of several organs during the early and late phases of embryogenesis, performing its function mainly by regulating the cell cycle and apoptosis pathways. The first pathogenic variant of HNF1B (namely, R177X) was reported in 1997 and is associated with the maturity-onset diabetes of the young. Since then, more than 230 different HNF1B variants have been reported, revealing a multifaceted syndrome with complex and heterogenous genetic, pathologic, and clinical profiles, mainly affecting the pediatric population. The pancreas and kidneys are the most frequently affected organs, resulting in diabetes, renal cysts, and a decrease in renal function, leading, in 2001, to the definition of HNF1B deficiency syndrome, including renal cysts and diabetes. However, several other organs and systems have since emerged as being affected by HNF1B defect, while diabetes and renal cysts are not always present. Especially, liver involvement has generally been overlooked but recently emerged as particularly relevant (mostly showing chronically elevated liver enzymes) and with a putative relation with tumor development, thus requiring a more granular analysis. Nowadays, HNF1B-associated disease has been recognized as a clinical entity with a broader and more variable multisystem phenotype, but the reasons for the phenotypic heterogeneity are still poorly understood. In this review, we aimed to describe the multifaceted nature of HNF1B deficiency in the pediatric and adult populations: we analyzed the genetic, phenotypic, and clinical features of this complex and misdiagnosed syndrome, covering the most frequent, unusual, and recently identified traits.

show abstract

HNF1B-MODY Masquerading as Type 1 Diabetes: A Pitfall in the Etiological Diagnosis of Diabetes

Cited by 7 publications

References 14 publications

Pancreatic Diseases: Genetics and Modeling Using Human Pluripotent Stem Cells

Pancreatic Diseases: Genetics and Modeling Using Human Pluripotent Stem Cells

Persistent hypomagnesaemia caused by HNF1B-MODY in a patient on platinum-based chemotherapy: A case report and review

The Landscape of HNF1B Deficiency: A Syndrome Not Yet Fully Explored

Contact Info

Product

Resources

About