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 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

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.

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

Maturity-onset diabetes of the young (MODY): an update

2015 ◽  
Vol 28 (3-4) ◽  
Author(s):  
Ahmet Anık ◽  
Gönül Çatlı ◽  
Ayhan Abacı ◽  
Ece Böber
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Young Adults ◽  
Maturity Onset Diabetes ◽  
Monogenic Disorders ◽  
Onset Diabetes ◽  
Dependent Form ◽  
Insulin Dependent

AbstractMaturity-onset diabetes of the young (MODY) is a group of monogenic disorders characterized by autosomal dominantly inherited non-insulin dependent form of diabetes classically presenting in adolescence or young adults before the age of 25 years. MODY is a rare cause of diabetes (1% of all cases) and is frequently misdiagnosed as Type 1 diabetes (T1DM) or Type 2 diabetes (T2DM). A precise molecular diagnosis is essential because it leads to optimal treatment of the patients and allows early diagnosis for their asymptomatic family members. Mutations in the glucokinase (

scholarly journals Pregnancy Complicated by Maternal MODY 3 and Paternal MODY 2 Diabetes and Subsequent Rapidly Falling Insulin Requirement

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Anastasia Mikuscheva ◽  
Adel Mekhail ◽  
Benjamin J. Wheeler
Keyword(s):  
Type 2 Diabetes ◽  
Pregnant Woman ◽  
Preterm Labour ◽  
Insulin Requirement ◽  
Monogenic Diabetes ◽  
Maturity Onset Diabetes ◽  
Insulin Requirements ◽  
Onset Diabetes

Background. ‘Maturity-Onset Diabetes of the Young’ (MODY) or monogenic diabetes accounts for approximately 1–2% of diabetes and is frequently misdiagnosed as type 1 or type 2 diabetes. Here we report a case of a 19-year-old pregnant woman with a MODY 3 diabetes expecting a child to a father with MODY 2 diabetes. Possible inheritance scenarios are described and the implications of these scenarios on the pregnancy and infant are discussed. In addition, the pregnancy was complicated by drastically falling insulin requirements in the mother in the 3rd trimester as well as preterm labour and delivery at 33+4 weeks of gestation.

scholarly journals Causal variants in Maturity Onset Diabetes of the Young (MODY) – A systematic review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ibrar Rafique ◽  
Asif Mir ◽  
Muhammad Arif Nadeem Saqib ◽  
Muhammad Naeem ◽  
Luc Marchand ◽  
...  
Keyword(s):  
Middle Eastern ◽  
Maturity Onset Diabetes ◽  
Dominant Type ◽  
Pathogenic Variants ◽  
Search Terms ◽  
Onset Diabetes ◽  
Causal Variants ◽  
Autosomal Dominant Type

Abstract Background Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant type of diabetes. Pathogenic variants in fourteen genes are reported as causes of MODY. Its symptoms overlap with type 1 and type 2 diabetes. Reviews for clinical characteristics, diagnosis and treatments are available but a comprehensive list of genetic variants, is lacking. Therefore this study was designed to collect all the causal variants involved in MODY, reported to date. Methods We searched PubMed from its date of inception to December 2019. The search terms we used included disease names and name of all the known genes involved. The ClinVar database was also searched for causal variants in the known 14 MODY genes. Results The record revealed 1647 studies and among them, 326 studies were accessed for full-text. Finally, 239 studies were included, as per our inclusion criteria. A total of 1017 variants were identified through literature review and 74 unpublished variants from Clinvar database. The gene most commonly affected was GCK, followed by HNF1a. The traditional Sanger sequencing was used in 76 % of the cases and 65 % of the studies were conducted in last 10 years. Variants from countries like Jordan, Oman and Tunisia reported that the MODY types prevalent worldwide were not common in their countries. Conclusions We expect that this paper will help clinicians interpret MODY genetics results with greater confidence. Discrepancies in certain middle-eastern countries need to be investigated as other genes or factors, like consanguinity may be involved in developing diabetes.

Quality of Life and Treatment Satisfaction in Participants with Maturity-Onset Diabetes of the Young: A Comparison to Other Major Forms of Diabetes

2020 ◽  
Author(s):  
Petra Dusatkova ◽  
Marketa Pavlikova ◽  
Alena Spirkova ◽  
Lenka Elblova ◽  
Denisa Janickova Zdarska ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Treatment Satisfaction ◽  
Genetic Diagnosis ◽  
Haemoglobin A1c ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes ◽  
Genetic Results

Abstract Aims We investigated the quality of life (QoL), treatment satisfaction and perception of genetic results in participants with Maturity-Onset Diabetes of the Young (MODY) and compared the results with those of subjects with type 1 (T1D) or type 2 (T2D) diabetes. Methods A total of 162 adults with GCK-MODY, 62 with HNF1A-MODY and 29 with HNF4A-MODY answered the questionnaire Audit of Diabetes Dependent Quality of Life, the Diabetes Treatment Satisfaction Questionnaire and non-validated instrument examining the respondent’s perception of the genetic results. Data from GCK-MODY patients were compared with 84 participants with T2D and HNF-MODY subjects were compared with 81 participants having T1D. Results Higher age (p=0.004), higher haemoglobin A1c (p=0.026) and medication (p=0.019) were associated with lower general QoL in GCK-MODY patients. In HNF-MODY patients, lower general QoL was associated with a longer time since diagnosis (p=0.005), worse haemoglobin bA1c (p=0.006) and insulin treatment (p=0.019). Similar numbers of participants with GCK- and HNF-MODY considered the genetic diagnosis of MODY to be positive, negative and without significance. The patient with GCK-MODY did not differ from those with T2D in terms of their QoL, but they were less satisfied with their treatment (p<0.001). QoL was better in patients with HNF-MODY compared with patients with T1D (p=0.006), and they did not differ in terms of treatment satisfaction. Conclusions QoL was affected in both GCK-MODY and HNF-MODY subjects. Apprehension of genetic diagnosis was not single-valued in MODY respondents.

scholarly journals Maturity-onset diabetes of the young: difficult differential diagnosis

2020 ◽  
Vol 4 (6) ◽  
pp. 372-376
Author(s):  
K.G. Lobanova ◽  
◽  
V.V. Titova ◽  
K.S. Dolgova ◽  
◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Differential Diagnosis ◽  
Genetic Testing ◽  
Molecular Genetic ◽  
Maturity Onset Diabetes ◽  
Molecular Genetic Testing ◽  
Onset Diabetes

Maturity-onset diabetes of the young (MODY) is a monogenic variant of diabetes characterized by the primary dysfunctions of pancreatic β-cells. MODY accounts for 1–2% of all variants of diabetes. MODY is generally associated with HNF1A gene mutation. The hallmarks of MODY are an autosomal dominant inheritance pattern, the onset of the disease in the young age, stable C-peptide level over a long period, the lack of the autoantibodies considered as the markers of diabetes, and the lack of ketoacidosis at disease onset. Considering that MODY manifests in children and young individuals, these patients are commonly diagnosed with type 1 diabetes. However, due to the atypical clinical signs of type 1 diabetes and the similarity of this disease to type 2 diabetes, these patients are often misdiagnosed with type 2 diabetes. This case report illustrates the differential diagnosis of diabetes in a patient with unusual disease course. The attention is focused on the features of MODY course. The indications to molecular genetic testing to verify the diagnosis are addressed.KEYWORDS: diabetes, maturity-onset diabetes of the young, monogenic diabetes, sulfonylureas, molecular genetic testing, LADA, pancreatogenic diabetes.FOR CITATION: Lobanova K.G., Titova V.V., Dolgova K.S. Maturity-onset diabetes of the young: difficult differential diagnosis. Russian Medical Inquiry. 2020;4(6):372–376. DOI: 10.32364/2587-6821-2020-4-6-372-376.

scholarly journals Maturity-onset diabetes of the young (MODY): Recognition is the need of the hour.

JMS SKIMS ◽  
2019 ◽  
Vol 22 (2) ◽  
Author(s):  
Javaid Bhat ◽  
Shariq Rashid Masoodi ◽  
Moomin Hussain Bhat
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Early Adulthood ◽  
Genetic Diagnosis ◽  
Dominant Mode ◽  
Maturity Onset Diabetes ◽  
Primary Defect ◽  
Onset Diabetes

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is characterized by autosomal dominant mode of inheritance, an early onset diabetes, mostly mild hyperglycemia as a result of a primary defect in pancreatic β-cell function. MODY represents less than 2% of all diabetes cases and is commonly misdiagnosed as type 1 or type 2 diabetes mellitus.  It is a genetically heterogeneous form of monogenic diabetes that is caused by mutations occurring in a number of different genes thus tends to cause a slightly different variant of diabetes. At least 14 MODY subtypes with distinct genetic etiologies have been identified to date. MODY is typically diagnosed during late childhood, adolescence, or early adulthood and is usually observed to develop in adults during their late 50's. One of the main drawbacks in its diagnosis is that many people with MODY are misdiagnosed as having type 1 or type 2 diabetes owing to low index of suspicion and lack of availability of genetic testing at affordable cost. However, a molecular and genetic diagnosis results in a better treatment and could also help in identifying other family members with MODY. A high index of suspicion is required to diagnose cases of MODY as misdiagnosis and inappropriate treatment may have a significant impact on quality of life (QOL) with increased cost and unnecessary treatment with insulin.

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