Clinical and Laboratory Characteristics of MODY (Maturity Onset Diabetes of Young) Cases, Genetic Mutation Spectrum and Phenotype-genotype Relationship (original) (raw)
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Maturity-onset diabetes of the young (MODY): Recognition is the need of the hour
J Med Sci, 2019
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...
Maturity-onset diabetes of the young (MODY): how many cases are we missing?
Diabetologia, 2010
Aims/hypothesis Maturity-onset diabetes of the young is frequently misdiagnosed as type 1 or type 2 diabetes. A correct diagnosis of MODY is important for determining treatment, but can only be confirmed by molecular genetic testing. We aimed to compare the regional distribution of confirmed MODY cases in the UK and to estimate the minimum prevalence. Methods UK referrals for genetic testing in 2,072 probands and 1,280 relatives between 1996 and 2009 were examined by region, country and test result. Referral rate and prevalence were calculated using UK Census 2001 figures. Results MODY was confirmed in 1,177 (35%) patients, with HNF1A (52%) and GCK mutations (32%) being most frequent in probands confirmed with MODY. There was considerable regional variation in proband referral rates (from <20 per million in Wales and Northern Ireland to >50 per million for South West England and Scotland) and patients diagnosed with MODY (5.3 per million in Northern Ireland, 48.9 per million in South West England). Referral rates and confirmed cases were highly correlated (r=0.96, p<0.0001). The minimum prevalence of MODY was estimated to be 108 cases per million. Conclusions/interpretation Assuming this minimal prevalence throughout the UK then >80% of MODY is not diagnosed by molecular testing. The marked regional variation in the prevalence of confirmed MODY directly results from differences in referral rates. This could reflect variation in awareness of MODY or unequal access to genetic testing. Increased referral for diagnostic testing is required if the majority of MODY patients are to have the genetic diagnosis necessary for optimal treatment.
Maturity onset diabetes of the young (MODY)—History, first case reports and recent advances
Gene, 2015
The world is seemingly facing a global increase in people suffering from diabetes especially in developing countries. The worldwide occurrence of diabetes for all age groups in year 2000 was estimated to be 2.8% and this number is most certainly expected to rise to 4.4% by 2030. Maturity-onset of diabetes of the young, or MODY, is a form of monogenic diabetes that is caused by mutations occurring in a number of different genes. Mutations in different genes tend to cause a slightly different variant of diabetes. 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. However, a molecular and genetic diagnosis can result in a better treatment and could also help in identifying other family members with MODY. This article explores the historical prospect and the genetic background of MODY, a brief summary of the first case reported and the significant factors that differentiate it from type 1 and type 2 diabetes.
Practical Diabetes International, 2001
The identification of five genes that can cause maturity onset diabetes of the young (MODY) means diagnostic and predictive genetic testing is now possible in 80% of MODY families. It is proposed that these recent classifications of diabetes 'genetic disorders of beta cell function' are recognised as separate disorders. Diagnostic genetic tests in those with diabetes will define the subtype, which has specific implications for treatment. In non-diabetic family members predictive tests can be used to test whether the mutated gene has been inherited, indicating >90% chance of developing diabetes.
2020
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.
Diagnosis and Treatment of MODY: An Updated Mini Review
Applied Sciences, 2021
Maturity-Onset Diabetes of the Young (MODY) is the most common form of monogenic diabetes resulting from a single gene mutation. It is characterized by mild hyperglycemia, autosomal dominant inheritance, early onset of diabetes (<25 years), insulin resistance, and preservation of endogenous insulin secretion. Currently, 14 MODY subtypes have been identified, with differences in incidence, clinical features, diabetes severity and related complications, and treatment response. This type of diabetes is mostly misdiagnosed as either type 1 or type 2 diabetes mellitus because it is difficult to differentiate between these forms of diabetes due to clinical similarities, the high cost of genetic testing, and lack of awareness. As a result, thousands of patients are not receiving appropriate treatment. Accurate diagnosis would allow for more effective therapeutic management and treatment strategies that are distinct from those used for type 1 and type 2 diabetes. This review serves to ex...
Archives of Endocrinology and Metabolism, 2022
Objetivo: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. Subjects and methods: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. Results: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. Conclusion: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes. Arch Endocrinol Metab.