Diagnosis and Treatment of MODY: An Updated Mini Review

Tshivhase, Abegail M; Matsha, Tandi E.; Raghubeer, Shanel

doi:10.3390/app11209436

Cited by 8 publications

(9 citation statements)

References 98 publications

(142 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most common non-neoplastic pancreatic diseases from the endocrine and exocrine lineages are diabetes and pancreatitis, respectively. netic defects in insulin secretion (37)(38)(39). Unlike T1D, MODY patients do not have autoantibodies, and unlike T2D, they are not usually obese and are not insulin-resistant (37)(38)(39).…”

Section: Hereditary Pancreatic Disordersmentioning

confidence: 99%

“…netic defects in insulin secretion (37)(38)(39). Unlike T1D, MODY patients do not have autoantibodies, and unlike T2D, they are not usually obese and are not insulin-resistant (37)(38)(39). MODY is inherited in an autosomal dominant manner, meaning that a single defective gene inherited from one parent is sufficient to cause the disorder (37)(38)(39).…”

Section: Hereditary Pancreatic Disordersmentioning

confidence: 99%

See 1 more Smart Citation

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: Hereditary Pancreatic Disordersmentioning

confidence: 99%

Section: Hereditary Pancreatic Disordersmentioning

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

“…HNF1B is a transcription factor of the homeodomain-containing transcription factor superfamily and is found in a wide range of tissues such as liver, intestine, stomach, lung, and pancreas. It is expressed in the early stage of embryonic development, being vital for the development of the nephron and the pancreas [ 6 ]. HNF1B contains 9 exons and is located on chromosome 17q12 [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Maturity-onset diabetes of the young secondary to HNF1B variants (HNF1B-MODY): a series of 10 patients from a single diabetes center

Amaral

Palha

Bogalho

et al. 2023

Diabetol Metab Syndr

View full text Add to dashboard Cite

Background Maturity-Onset Diabetes of the Young (MODY) is an autosomal dominant condition and represents 1–5% of all cases of diabetes mellitus. MODY is often misdiagnosed as type 1 or type 2 diabetes. The rare subtype 5 (HNF1B-MODY) is due to hepatocyte nuclear factor 1β (HNF1B) molecular alteration and is remarkable for its multisystemic phenotypes characterized by a broad spectrum of pancreatic and extra-pancreatic clinical manifestations. Methods Retrospective study of patients with HNF1B-MODY diagnosis followed in the Centro Hospitalar Universitário Lisboa Central (Lisbon, Portugal). Demographic data, medical history, clinical and laboratory data, follow-up and treatment procedures were obtained from electronic medical records. Results We found 10 patients with HNF1B variants (7 index cases). The median age at diabetes diagnosis was 28 (IQR 24) years and the median age at HNF1B-MODY diagnosis was 40.5 (IQR 23) years. Six patients were initially misclassified as type 1 and 4 as type 2 diabetes. The average time between diabetes diagnosis and the diagnosis of HNF1B-MODY was 16.5 years. Diabetes was the first manifestation in half of the cases. The other half presented with kidney malformations and chronic kidney disease at pediatric age as the first manifestation. All these patients were submitted to kidney transplantation. Long-term diabetes complications included retinopathy (4/10), peripheral neuropathy (2/10) and ischemic cardiomyopathy (1/10). Other extra-pancreatic manifestations included liver test alterations (4/10) and congenital malformation of the female reproductive tract (1/6). History of a first-degree relative with diabetes and/or nephropathy diagnosed at a young age was present in 5 of the 7 index cases. Conclusions Despite being a rare disease, HNF1B-MODY is underdiagnosed and often misclassified. It should be suspected in patients with diabetes and CKD, especially when diabetes appears at a young age, a family history is present, and nephropathy appears before/shortly after the diagnosis of diabetes. Presence of unexplained liver disease increases the degree of suspicion for HNF1B-MODY. Early diagnosis is important to minimize complications and to allow familial screening and pre-conception genetic counseling. Trial registration not applicable due to the retrospective nature of the study, non-interventional.

show abstract

“…(1) The diagnostic criteria of the Practice Guideline for MODY in 2008 comprise early onset of diabetes before 25 years of age, history of diabetes in two consecutive generations, absence of pancreatic β-cell autoimmunity, and preserved β-cell function defined by the lack of insulin treatment or serum C-peptide levels > 200 pmol/L after 3 years of insulin therapy (2) To date, at least 14 distinct MODY subtypes have been identified according to single gene mutations inherited by autosomal dominant pattern, and involved in the differentiation, development and function of β-cells. (3,4) Such heterogeneity significantly impacts diabetes pathophysiology, clinical course and treatment response, which highly differ among all MODY forms. (5) Ranging from 80% to 95% of MODY cases the underlying cause involves the pathogenetic variants of hepatocyte nuclear factor-1 homeobox A (HNF1A), hepatocyte nuclear factor-4 homeobox A (HNF4A), hepatocyte nuclear factor-1 homeobox B (HNF1B) and glucokinase (GCK) genes.…”

Section: Introductionmentioning

confidence: 99%

“…(5) Ranging from 80% to 95% of MODY cases the underlying cause involves the pathogenetic variants of hepatocyte nuclear factor-1 homeobox A (HNF1A), hepatocyte nuclear factor-4 homeobox A (HNF4A), hepatocyte nuclear factor-1 homeobox B (HNF1B) and glucokinase (GCK) genes. (3,6) However, despite the molecular evidence, up to 11% of MODY has unknown Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content.…”

Section: Introductionmentioning

confidence: 99%

Moody Only Monogenic? A Narrative Review of the Rare and Low-Penetrant Genetic Variants

Hasballa,

Maggi

2023

Preprint

View full text Add to dashboard Cite

Introduction: Maturity-onset diabetes of the young (MODY) represents the most frequent form of monogenic diabetes mellitus (DM), currently classified in 14 distinct subtypes according to single gene mutations involved in the differentiation and function of pancreatic β-cells. Case report: The female patient at the age of 16 years old was diagnosed with non-autoimmune DM with glycated haemoglobin (HbA1c) value of 6.5%. After 6 years of dietary and lifestyle interventions due to the worsening of the glycometabolic profile, oral hypoglicemic therapy was initiated including at first only metformin, and subsequently also sulfonylureas and DPP-IV inhibitor. 11 years after diagnosis glargine insulin was started, associated 3 years later with Lispro insulin because of the worsening of the post-prandial glycaemia. According to the genetic testing a compound heterozygosis of two novel variants of uncertain/unknown clinical significance of BLK and RFX6 genes, respectively c.1013T>C (Ile338Thr) and c.1072G>A (Val358Ile), was identified. The RFX6 variant was also detected in the patient’s mother genome, while the BLK variant in her father’s. Discussion: Up to 11% of MODY has unknown etiology, suggesting that the genetic landscape is still to be explored. Recently, novel causal genes, involved in the differentiation and function of β-cells, have been identified such as RFX6, NKX2.2, NKX6.1, WFS1 and PCBD1. Genetic and clinical features of MODY variants remain highly heterogeneous, with no direct genotype-phenotype correlation especially in the low-penetrant subtypes. Thus, the aim of our paper is to present additionally to such rare case of a compound heterozygosity BLK/RFX6 underlying MODY, also a brief review of literature focused on the rare and reduced-penetrant variants, as well as on some controversies regarding this subtype of monogenic diabetes. Conclusions: Due to the limited data available, the assessment of MODY related-genes pathogenicity remains challenging especially in the setting of rare and low-penetrant subtypes. In consideration of the crucial importance of an accurate diagnosis, prognosis and management of MODY, more studies are warranted to further investigate its genetic landscape, the genotype-phenotype correlation, as well as the pathogenetic contribution of the non-genetic modifiers in this cohort of patients.

show abstract

Diagnosis and Treatment of MODY: An Updated Mini Review

Cited by 8 publications

References 98 publications

Pancreatic Diseases: Genetics and Modeling Using Human Pluripotent Stem Cells

Pancreatic Diseases: Genetics and Modeling Using Human Pluripotent Stem Cells

Maturity-onset diabetes of the young secondary to HNF1B variants (HNF1B-MODY): a series of 10 patients from a single diabetes center

Moody Only Monogenic? A Narrative Review of the Rare and Low-Penetrant Genetic Variants

Contact Info

Product

Resources

About