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.

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 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.

Maturity onset diabetes of the young

2021 ◽  
pp. 175573802110395
Author(s):  
Muhammad Yassir Yaqub Qureshi ◽  
Rabia Nawaz
Keyword(s):  
Primary Care Physicians ◽  
Genetic Disorder ◽  
Single Gene ◽  
Treatment Options ◽  
Maturity Onset Diabetes ◽  
Rare Disorders ◽  
Onset Diabetes ◽  
Success Of Treatment

GPs not only diagnose common metabolic and endocrine conditions, but also must recognise rare disorders and ultimately offer accurate diagnoses with appropriate investigations. In cases where treatment options exist, an early diagnosis is often crucial to the success of treatment and the possibility of reversing or stalling progressive symptoms. Maturity onset diabetes of the young (MODY) is a rare form of diabetes, which is different from type 1 and type 2 diabetes mellitus (DM) and characterised by a single gene ‘monogenic’ mutation with autosomal-dominant inheritance. It is estimated that approximately 80% of patients with MODY are initially misdiagnosed with type 1 or type 2 DM, and awareness of this condition among primary care physicians should improve diagnosis. The aim of this article is to present basic information about this rare, but rather important, genetic disorder that is linked to diabetes in younger people.

scholarly journals Maturity Onset Diabetes of the Young due to Glucokinase, HNF1-A, HNF1-B, and HNF4-A Mutations in a Cohort of Turkish Children Diagnosed as Type 1 Diabetes Mellitus

2018 ◽  
Vol 90 (4) ◽  
pp. 257-265 ◽  
Author(s):  
Elif Ozsu ◽  
Filiz Mine Cizmecioglu ◽  
Gul Yesiltepe Mutlu ◽  
Aysegul Bute Yuksel ◽  
Mursel Calıskan ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Rare Condition ◽  
High Sensitivity ◽  
Genetic Mutation ◽  
Nuclear Factor ◽  
Maturity Onset Diabetes ◽  
Hepatocyte Nuclear Factor ◽  
Turkish Children ◽  
Onset Diabetes

Background/Aims: Maturity onset diabetes of the young (MODY) is a rare condition often misdiagnosed as type 1 diabetes (T1D). The purposes of this study were: to identify any patients followed in a large Turkish cohort as T1D, with an atypical natural history, who may in fact have MODY, and to define the criteria which would indicate patients with likely MODY as early as possible after presentation to allow prompt genetic testing. Methods: Urinary C-peptide/creatinine ratio (UCPCR) was studied in 152 patients having a diagnosis of T1D for at least 3 years. Those with a UCPCR ≥0.2 nmol/mmol were selected for genetic analysis of the Glucokinase (GCK), Hepatocyte nuclear factor 1a (HNF1A), Hepatocyte nuclear factor 4a (HNF4A), and Hepatocyte nuclear factor 1b (HNF1B) genes. This UCPCR cut-off was used because of the reported high sensitivity and specificity. Cases were also evaluated using a MODY probability calculator. Results: Twenty-three patients from 152 participants (15.1%) had a UCPCR indicating persistent insulin reserve. The mean age ± SD of the patients was 13.6 ± 3.6 years (range 8.30–21.6). Of these 23, two (8.7%) were found to have a mutation, one with HNF4A and one with HNF1B mutation. No mutations were detected in the GCK or HNF1A genes. Conclusion: In Turkish children with a diagnosis of T1D but who have persistent insulin reserve 3 years after diagnosis, up to 9% may have a genetic mutation indicating a diagnosis of MODY.

scholarly journals 21-Year-Old Pregnant Woman with MODY-5 Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Anastasia Mikuscheva ◽  
Elliot McKenzie ◽  
Adel Mekhail
Keyword(s):  
Type 2 Diabetes ◽  
Pregnant Woman ◽  
Correct Diagnosis ◽  
Monogenic Diabetes ◽  
Maturity Onset Diabetes ◽  
Renal Anomalies ◽  
Family History Of Diabetes ◽  
History Of

The term “Maturity-Onset Diabetes of the Young” (MODY) was first described in 1976 and is currently referred to as monogenic diabetes. There are 14 known entities accounting for 1-2% of diabetes and they are frequently misdiagnosed as either type 1 or type 2 diabetes. MODY-5 is an entity of monogenic diabetes that is associated with genitourinary malformations and should be considered by obstetricians in pregnant women with a screen positive for diabetes, genitourinary malformations, and fetal renal anomalies. Correct diagnosis of monogenic diabetes has implications on managing patients and their families. We are reporting a case of a 21-year-old pregnant woman with a bicornuate uterus, fetal renal anomalies, and a family history of diabetes that were suggestive of a MODY-5 diabetes.

scholarly journals Mutations at the BLK locus linked to maturity onset diabetes of the young and  -cell dysfunction

2009 ◽  
Vol 106 (34) ◽  
pp. 14460-14465 ◽  
Author(s):  
M. Borowiec ◽  
C. W. Liew ◽  
R. Thompson ◽  
W. Boonyasrisawat ◽  
J. Hu ◽  
...  
Keyword(s):  
Maturity Onset Diabetes ◽  
Cell Dysfunction ◽  
Onset Diabetes

Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing

2016 ◽  
Vol 29 (4) ◽  
Author(s):  
Sebahat Yılmaz Ağladıoğlu ◽  
Zehra Aycan ◽  
Semra Çetinkaya ◽  
Veysel Nijat Baş ◽  
Aşan Önder ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Next Generation Sequencing ◽  
Point Mutations ◽  
Maturity Onset Diabetes ◽  
Turkish Children ◽  
Onset Diabetes ◽  
Molecular Studies ◽  
Generation Sequencing

AbstractMaturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11A panel of 11We identified 28 (65%) point mutations among 43 patients. Eighteen patients haveThis is the first study including molecular studies of 11

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