scholarly journals The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY)

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Ken Munene Nkonge ◽  
Dennis Karani Nkonge ◽  
Teresa Njeri Nkonge
Keyword(s):  
De Novo ◽  
Middle Eastern ◽  
Treatment Options ◽  
Relevant Literature ◽  
Diagnosis And Treatment ◽  
Endocrine Disorders ◽  
Main Body ◽  
Maturity Onset Diabetes ◽  
De Novo Mutations ◽  
Onset Diabetes

Abstract Background The most common type of monogenic diabetes is maturity-onset diabetes of the young (MODY), a clinically and genetically heterogeneous group of endocrine disorders that affect 1–5% of all patients with diabetes mellitus. MODY is characterized by autosomal dominant inheritance but de novo mutations have been reported. Clinical features of MODY include young-onset hyperglycemia, evidence of residual pancreatic function, and lack of beta cell autoimmunity or insulin resistance. Glucose-lowering medications are the main treatment options for MODY. The growing recognition of the clinical and public health significance of MODY by clinicians, researchers, and governments may lead to improved screening and diagnostic practices. Consequently, this review article aims to discuss the epidemiology, pathogenesis, diagnosis, and treatment of MODY based on relevant literature published from 1975 to 2020. Main body The estimated prevalence of MODY from European cohorts is 1 per 10,000 in adults and 1 per 23,000 in children. Since little is known about the prevalence of MODY in African, Asian, South American, and Middle Eastern populations, further research in non-European cohorts is needed to help elucidate MODY’s exact prevalence. Currently, 14 distinct subtypes of MODY can be diagnosed through clinical assessment and genetic analysis. Various genetic mutations and disease mechanisms contribute to the pathogenesis of MODY. Management of MODY is subtype-specific and includes diet, oral antidiabetic drugs, or insulin. Conclusions Incidence and prevalence estimates for MODY are derived from epidemiologic studies of young people with diabetes who live in Europe, Australia, and North America. Mechanisms involved in the pathogenesis of MODY include defective transcriptional regulation, abnormal metabolic enzymes, protein misfolding, dysfunctional ion channels, or impaired signal transduction. Clinicians should understand the epidemiology and pathogenesis of MODY because such knowledge is crucial for accurate diagnosis, individualized patient management, and screening of family members.

scholarly journals Maturity onset diabetes of the young: Diagnosis and treatment options

2016 ◽  
Vol 5 (4) ◽  
pp. e0402
Author(s):  
Serghei Covanțev ◽  
Andrian Chiriac ◽  
Ludmila Perciuleac ◽  
Vladlena Zozina
Keyword(s):  
Treatment Options ◽  
Diagnosis And Treatment ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes

scholarly journals Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

2021 ◽  
Vol 22 (14) ◽  
pp. 7553
Author(s):  
Dawid Skoczek ◽  
Józef Dulak ◽  
Neli Kachamakova-Trojanowska
Keyword(s):  
Clinical Symptoms ◽  
Treatment Options ◽  
Correct Diagnosis ◽  
Vascular Complications ◽  
Disease Modelling ◽  
Endocrine Disorders ◽  
Maturity Onset Diabetes ◽  
Cell Dysfunction ◽  
Onset Diabetes

Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous group of monogenic endocrine disorders that is characterised by autosomal dominant inheritance and pancreatic β-cell dysfunction. These patients are commonly misdiagnosed with type 1 or type 2 diabetes, as the clinical symptoms largely overlap. Even though several biomarkers have been tested none of which could be used as single clinical discriminator. The correct diagnosis for individuals with MODY is of utmost importance, as the applied treatment depends on the gene mutation or is subtype-specific. Moreover, in patients with HNF1A-MODY, additional clinical monitoring can be included due to the high incidence of vascular complications observed in these patients. Finally, stratification of MODY patients will enable better and newer treatment options for MODY patients, once the disease pathology for each patient group is better understood. In the current review the clinical characteristics and the known disease-related abnormalities of the most common MODY subtypes are discussed, together with the up-to-date applied diagnostic criteria and treatment options. Additionally, the usage of pluripotent stem cells together with CRISPR/Cas9 gene editing for disease modelling with the possibility to reveal new pathophysiological mechanisms in MODY is discussed.

Review of treatment and therapeutic targets in brain arteriovenous malformation

2021 ◽  
pp. 0271678X2110267
Author(s):  
Peipei Pan ◽  
Shantel Weinsheimer ◽  
Daniel Cooke ◽  
Ethan Winkler ◽  
Adib Abla ◽  
...  
Keyword(s):  
Animal Models ◽  
De Novo ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Therapeutic Targets ◽  
Current Treatment ◽  
Mitogen Activated Protein Kinase ◽  
De Novo Mutations ◽  
Genetic Syndromes ◽  
Mitogen Activated Protein

Brain arteriovenous malformations (bAVM) are an important cause of intracranial hemorrhage (ICH), especially in younger patients. The pathogenesis of bAVM are largely unknown. Current understanding of bAVM etiology is based on studying genetic syndromes, animal models, and surgically resected specimens from patients. The identification of activating somatic mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene and other mitogen-activated protein kinase ( MAPK) pathway genes has opened up new avenues for bAVM study, leading to a paradigm shift to search for somatic, de novo mutations in sporadic bAVMs instead of focusing on inherited genetic mutations. Through the development of new models and understanding of pathways involved in maintaining normal vascular structure and functions, promising therapeutic targets have been identified and safety and efficacy studies are underway in animal models and in patients. The goal of this paper is to provide a thorough review or current diagnostic and treatment tools, known genes and key pathways involved in bAVM pathogenesis to summarize current treatment options and potential therapeutic targets uncovered by recent discoveries.

Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options

Endocrines ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 485-501
Author(s):  
Zoltan Antal
Keyword(s):  
Clinical Presentation ◽  
Clinical Symptoms ◽  
Treatment Options ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes ◽  
Inappropriate Treatment ◽  
Monogenic Forms Of Diabetes ◽  
Initial Description

Maturity Onset Diabetes of the Young (MODY) encompasses a group of rare monogenic forms of diabetes distinct in etiology and clinical presentation from the more common forms of Type 1 (autoimmune) and Type 2 diabetes. Since its initial description as a clinical entity nearly 50 years ago, the underlying genetic basis for the various forms of MODY has been increasingly better elucidated. Clinically, the diagnosis may be made in childhood or young adulthood and can present as overt hyperglycemia requiring insulin therapy or as a subtle form of slowly progressive glucose impairment. Due to the heterogeneity of clinical symptoms, patients with MODY may be misdiagnosed as possessing another form of diabetes, resulting in potentially inappropriate treatment and delays in screening of affected family members and associated comorbidities. In this review, we highlight the various known genetic mutations associated with MODY, clinical presentation, indications for testing, and the treatment options available.

scholarly journals De Novo Mutations in EIF2B1 Affecting eIF2 Signaling Cause Neonatal/Early-Onset Diabetes and Transient Hepatic Dysfunction

Diabetes ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 477-483 ◽  
Author(s):  
Elisa De Franco ◽  
Richard Caswell ◽  
Matthew B. Johnson ◽  
Matthew N. Wakeling ◽  
Amnon Zung ◽  
...  
Keyword(s):  
Early Onset ◽  
Hepatic Dysfunction ◽  
De Novo ◽  
De Novo Mutations ◽  
Onset Diabetes

scholarly journals A Review of Von Hippel-Lindau Syndrome

2017 ◽  
Vol 4 (3) ◽  
pp. 20-29 ◽  
Author(s):  
Neha Varshney ◽  
Amanuel A Kebede ◽  
Harry Owusu-Dapaah ◽  
Jason Lather ◽  
Manu Kaushik ◽  
...  
Keyword(s):  
De Novo ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Positive Family History ◽  
Treatment Modalities ◽  
Pancreatic Cysts ◽  
Molecular Testing ◽  
De Novo Mutations ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Syndrome

Von Hippel-Lindau syndrome (VHL) is a familial neoplastic condition seen in approximately 1 in 36,000 live births. It is caused by germline mutations of the tumor suppressor gene VHL, located on the short arm of chromosome 3. While the majority of the affected individuals have a positive family history, up to 20% of cases arise from de novo mutations. VHL syndrome is characterized by the presence of benign and malignant tumors affecting the central nervous system, kidneys, adrenals, pancreas, and reproductive organs. Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; renal cell carcinoma; pancreatic cysts and neuroendocrine tumors; and endolymphatic sac tumors. Diagnosis of VHL is prompted by clinical suspicion and confirmed by molecular testing. Management of VHL patients is complex and multidisciplinary. Routine genetic testing and surveillance using various diagnostic techniques are used to help monitor disease progression and implement treatment options. Despite recent advances in clinical diagnosis and management, life expectancy for VHL patients remains low at 40–52 years. This article provides an overview of the major clinical, histological, and radiological findings, as well as treatment modalities.

Phenotype of a patient with a de novo mutation in the hepatocyte nuclear factor 1β/maturity-onset diabetes of the young type 5 gene

Metabolism ◽  
2008 ◽  
Vol 57 (3) ◽  
pp. 416-420 ◽  
Author(s):  
Christof Mayer ◽  
Yvonne Böttcher ◽  
Peter Kovacs ◽  
Jan Halbritter ◽  
Michael Stumvoll
Keyword(s):  
De Novo ◽  
De Novo Mutation ◽  
Nuclear Factor ◽  
Maturity Onset Diabetes ◽  
Hepatocyte Nuclear Factor ◽  
Onset Diabetes
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