scholarly journals Monogenic diabetes mellitus and clinical implications of genetic diagnosis

2021 ◽  
Vol 5 (3) ◽  
pp. 106-116
Author(s):  
Eungu Kang ◽  
Lindsey Yoojin Chung ◽  
Yu Jin Kim ◽  
Kyung Eun Oh ◽  
Young-Jun Rhie
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Clinical Implications ◽  
High Dose ◽  
Activating Mutations ◽  
Β Cell Function

Monogenic diabetes mellitus, which is diabetes caused by a defect in a single gene that is associated with β cell function or insulin action, accounts for 1% to 6% of all pediatric diabetes cases. Accurate diagnosis is important, as the effective treatment differs according to genetic etiology in some types of monogenic diabetes: high-dose sulfonylurea treatment in neonatal diabetes caused by activating mutations in KCNJ11 or ABCC8; low-dose sulfonylurea treatment in HNF1A/HNF4A-diabetes; and no treatment in GCK diabetes. Monogenic diabetes should be suspected by clinicians for certain combinations of clinical features and laboratory results, and approximately 80% of monogenic diabetes cases are misdiagnosed as type 1 diabetes or type 2 diabetes. Here, we outline the types of monogenic diabetes and the clinical implications of genetic diagnosis.

Neonatal Diabetes – From Gene Discovery yo Clinical Practice Changes

2013 ◽  
Vol 20 (3) ◽  
pp. 343-352
Author(s):  
Cristian Guja ◽  
Loreta Guja ◽  
Constantin Ionescu-Tîrgovişte
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Single Gene ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Special Focus ◽  
Sulphonylurea Treatment ◽  
The Common

Abstract Diabetes mellitus is one of the most common chronic diseases but also one of the most heterogeneous. Apart the common phenotypes of type 1 and type 2 diabetes, around 1-2% of all cases arise from a single gene mutation and are known as monogenic diabetes. Diabetes diagnosed within the first 6 months of life is known as neonatal diabetes and has been extensively studied during the last two decades. Unraveling the genetic cause and molecular mechanism of this rare diabetes phenotype led to a dramatic change in the treatment of these children who often can be switched from insulin to sulphonylurea treatment. The aim of this paper is to review the known genetic causes of neonatal diabetes and to highlight the most recent aspects of the disease caused by mutations in the KATP and insulin genes, with a special focus on the individualized treatment of these cases

A case of monogenic diabetes mellitus caused by a novel heterozygous RFX6 nonsense mutation in a 14-year-old girl

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Goo Lyeon Kim ◽  
Soo Heon Kwak ◽  
Jeesuk Yu
Keyword(s):  
Diabetes Mellitus ◽  
Nonsense Mutation ◽  
Pancreatic Beta Cells ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Monogenic Diabetes ◽  
Islet Autoantibody ◽  
Type 2 Dm ◽  
Long Acting

Abstract Objectives Monogenic diabetes mellitus (DM) is a single gene disorder, primarily characterized by impairment in the development or function of pancreatic beta cells. Case presentation A 14-year-old girl was initially diagnosed with type 2 DM. The patient did not have any anti-islet autoantibody and showed acanthosis nigricans. She was managed with long-acting insulin and oral hypoglycemic agent, but HbA1c was still 9.3% after 1 year of management. Her mother already had type 2 DM at 46-year-old and was on medication. Under the possibility of familial monogenic DM, targeted exome sequencing was performed which included 29 genes associated with monogenic DM. Nonsense mutation of the gene RFX6 (c.2661T>A, p.Tyr887∗) was found. After adding Glucagon-like peptide-1 (GLP-1) receptor agonist, HbA1c improved from 8.8 to 6.8% and body mass index (BMI) also improved from 31.0 to 29.2 kg/m2. Conclusions It may be worth investigating genetic etiology in early-onset autoantibody-negative DM for specific genetic diagnosis and better management.

scholarly journals Severe Dental Disease as a Presenting Sign of Relapsed 6q24-Related Transient Neonatal Diabetes Mellitus

2020 ◽  
Vol 2020 ◽  
pp. 1-3
Author(s):  
Anna Delamerced ◽  
Lauren J. Massingham ◽  
Jose Bernardo Quintos
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
First Year ◽  
Dental Disease ◽  
Transient Neonatal Diabetes Mellitus ◽  
Chromosome 6Q24 ◽  
Β Cell Function ◽  
Transient Neonatal Diabetes

Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes that presents in infancy and is characterized by intrauterine growth restriction and hyperglycemia without ketones on urinalysis. Patients are treated with insulin until remission, usually within the first year. Relapse to a permanent state may occur later in life, with a mean age of 14 years. The most common cause of TNDM is a chromosome 6q24 mutation that affects pancreatic β-cell function. Reports of relapse have been limited. We describe a case of an adolescent female with TNDM due to 6q24 hypomethylation who relapsed at 15 years of age with severe dental disease as the presenting sign.

Longitudinal Glycaemic Profiles during Remission in 6q24-Related Transient Neonatal Diabetes Mellitus

2021 ◽  
Vol 94 (5-6) ◽  
pp. 229-234
Author(s):  
Yasuhiro Sato ◽  
Tsuyoshi Isojima ◽  
Kiyomi Takamiya ◽  
Kahoko Motoyama ◽  
Shigehiro Enkai ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Neonatal Diabetes ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Β Cell ◽  
Transient Neonatal Diabetes Mellitus ◽  
Glucose Intake ◽  
Β Cell Function ◽  
Transient Neonatal Diabetes

<b><i>Introduction:</i></b> Transient neonatal diabetes mellitus (TNDM) is a rare condition that is characterized by the presence of diabetes mellitus during the first 6 months of life and remission by 18 months of age. It usually relapses at a median age of 14 years. Hyperinsulinaemic hypoglycaemia is a relatively common complication during remission. Although β-cell function is reported to be impaired at relapse, the clinical course of glycaemic profiles during remission in patients with TNDM remains largely unknown. <b><i>Case Presentation:</i></b> Longitudinal glycaemic profiles were investigated annually from remission (185 days) to relapse (14.5 years) in a patient with TNDM due to paternal 6q24 duplication using the oral glucose tolerance test (glucose intake: 1.75 g/kg to a maximum of 75 g). The patient’s β-cell function and insulin sensitivity were assessed by calculating the insulinogenic index, homeostasis model assessment of β-cell function (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index, and Matsuda index. Early insulin response to glucose intake was impaired throughout remission, whereas fasting insulin and β-cell function by HOMA-β gradually increased in the first few years since remission, followed by a gradual decline in function. In contrast, HOMA-IR fluctuated and peaked at 6.5 years of age. <b><i>Conclusion:</i></b> This is the first report of annual longitudinal glycaemic profiles in a patient with 6q24-related TNDM during remission. We identified fluctuations in β-cell function and insulin resistance during remission.

scholarly journals A RARE CASE OF A YOUNG INFANT WITH MONOGENIC DIABETES MELLITUS AND CENTRAL VENOUS SINUS THROMBOSIS

2020 ◽  
pp. 32-33
Author(s):  
Payal Patil ◽  
Rajesh Kulkarni ◽  
Aarti Kinikar
Keyword(s):  
Diabetes Mellitus ◽  
Autosomal Dominant ◽  
Sinus Thrombosis ◽  
Single Gene ◽  
Young Infant ◽  
Neonatal Diabetes ◽  
Female Child ◽  
Monogenic Diabetes ◽  
Permanent Neonatal Diabetes ◽  
Glucose Levels

Diabetes mellitus is a metabolic disease characterised by chronically high glucose levels. Genetic factors have been implicated in the etiology following mutations in a single gene. An extremely rare form of diabetes mellitus is monogenic diabetes, a subset of which is permanent neonatal diabetes which is usually suspected in a child less than 6 months presenting with hyperglycaemia. We are reporting case of a 40 days old female child with an autosomal dominant INS gene mutation which results in permanent neonatal diabetes in infants requiring lifelong insulin therapy.

Successful transition to sulfonylurea therapy in two Iraqi siblings with neonatal diabetes mellitus and iDEND syndrome due to ABCC8 mutation

2016 ◽  
Vol 29 (12) ◽  
Author(s):  
Elif Ozsu ◽  
Dinesh Giri ◽  
Gulcan Seymen Karabulut ◽  
Senthil Senniappan
Keyword(s):  
Diabetes Mellitus ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
The Other ◽  
Rare Form ◽  
Successful Transition ◽  
Activating Mutations ◽  
Chromosome 6Q24

Abstract Neonatal diabetes is a rare form of monogenic diabetes characterised by persistent hyperglycaemia during the first 6–9 months of age. About half of the cases of neonatal diabetes are transient forms resulting from mutations in the genes in the imprinted region of chromosome 6q24 and the other half are permanent forms. Activating mutations in the potassium ATP (K

Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine

2020 ◽  
Vol 16 (8) ◽  
pp. 807-819 ◽  
Author(s):  
Madalena Sousa ◽  
Jácome Bruges-Armas
Keyword(s):  
Diabetes Mellitus ◽  
Complex Disease ◽  
Clinical Manifestations ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Diabetes Genetics ◽  
Individualize Treatment

Background: Diabetes mellitus (DM) is a complex disease with significant impression in today's world. Aside from the most common types recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM), recent studies have emphasized the crucial role of genetics in DM, allowing the distinction of monogenic diabetes. Methods: Authors did a literature search with the purpose of highlighting and clarifying the subtypes of monogenic diabetes, as well as the accredited genetic entities responsible for such phenotypes. Results: The following subtypes were included in this literature review: maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM) and maternally inherited diabetes and deafness (MIDD). So far, 14 subtypes of MODY have been identified, while three subtypes have been identified in NDM - transient, permanent, and syndromic. Discussion: Despite being estimated to affect approximately 2% of all the T2DM patients in Europe, the exact prevalence of MODY is still unknown, accentuating the need for research focused on biomarkers. Consequently, due to its impact in the course of treatment, follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Conclusion: Currently, advances in the genetics field allowed the recognition of new DM subtypes, which until now, were considered slight variations of the typical forms. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations, to facilitate diagnosis and individualize treatment.

The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene

2020 ◽  
Vol 33 (12) ◽  
pp. 1605-1608
Author(s):  
Xiao Qin ◽  
Jingzi Zhong ◽  
Dan Lan
Keyword(s):  
Diabetes Mellitus ◽  
Novel Mutation ◽  
Male Infant ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Rare Form ◽  
Case Presentation ◽  
Abcc8 Gene

AbstractObjectivesNeonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes that is usually diagnosed in the first six months of life.Case presentationWe report on a male infant with neonatal diabetes who presented with diabetic ketoacidosis at two months and 16 days. A novel homozygous missense mutation (c.259T>G) was identified in the ABCC8 gene. In this case, insulin was replaced with glimepiride at a dosage of 0.49 mg/kg/day at five months, and this achieved metabolic control and satisfactory growth as observed at follow-up.ConclusionsThis report improves our understanding of the mutational spectrum of ABCC8, which is normally associated with NDM, and shows that the treatment regimen for this condition can be successfully switched from insulin therapy to the use of sulfonylurea.

scholarly journals Post-Transplant Diabetes Mellitus and Prediabetes in Renal Transplant Recipients: An Update

Nephron ◽  
2021 ◽  
pp. 1-13
Author(s):  
Ana Elena Rodríguez-Rodríguez ◽  
Esteban Porrini ◽  
Mads Hornum ◽  
Javier Donate-Correa ◽  
Raúl Morales-Febles ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Renal Transplant ◽  
Cell Function ◽  
Cell Damage ◽  
Current Evidence ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Β Cell Function

Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20–30% of renal transplant recipients and increases the risk for cardiovascular and infectious events. Thus, understanding pathogenesis of PTDM would help limiting its consequences. In this review, we analyse novel aspects of PTDM, based on studies of the last decade, such as the clinical evolution of PTDM, early and late, the reversibility rate, diagnostic criteria, risk factors, including pre-transplant metabolic syndrome and insulin resistance (IR) and the interaction between these factors and immunosuppressive medications. Also, we discuss novel pathogenic factors, in particular the role of β-cell function in an environment of IR and common pathways between pre-existing cell damage and tacrolimus-induced toxicity. The relevant role of prediabetes in the pathogenesis of PTDM and cardiovascular disease is also addressed. Finally, current evidence on PTDM treatment is discussed.

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