Phenotypical aspects of maturity‐onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database

Schober, Edith; Rami, Birgit; Grabert, M.; Thon, A.; Kapellen, Th.; Reinehr, T.; Holl, Reinhard W.

doi:10.1111/j.1464-5491.2009.02720.x

Cited by 164 publications

(134 citation statements)

References 36 publications

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“…This difference only nearly attained statistical significance, but supports the fact that mutations found in the transactivation domain were mostly nonsense or frameshift as well as the possibility that these patients may have had more severe clinical phenotypes, requiring insulin more often. Others studies also found a fairly high proportion of patients with more severe clinical phenotypes resulting from HNF1A mutations to use insulin treatment and that with disease progression, (15,16). Mutation isoform and domain of occurrence associated with age at disease onset in certain studies examining larger numbers and older subjects.…”

Section: Discussionmentioning

confidence: 99%

Genetic and clinical characteristics of patients with HNF1A gene variations from the German–Austrian DPV database

Awa

Thon²,

Raile³

et al. 2011

European Journal of Endocrinology

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Objective: To determine prevalence, genetic and phenotype characteristics of patients with hepatocyte nuclear factor-1a (HNF1A) variants in the Diabetes Patienten Verlaufsdokumenation (DPV) multicentre database and to examine the influence of HNF1A mutation type, or location on clinical phenotypes. Patients and methods: Seventy-one DPV patients were labelled as HNF1A-MODY (MODY3). Forty-four patients carried HNF1A mutations, while 27 patients were found to have HNF1A polymorphisms only. Associations between mutation type/position and age at disease onset, HbAlc, body mass index (BMI), diagnosis, family history and treatment modality were analysed using non-parametric statistics (Wilcoxon test). Results: Patients with HNF1A mutations were 36% male, aged 14.1G5.8 years at diagnosis, and slightly overweight (BMI-SDS: C0.8G1.1). Treatment was lifestyle intervention (20.5%), insulin (35.3%), oral anti-diabetic (OAD, 43%) and both insulinCOAD (15.9%). More patients with missense mutations (60%) than patients with nonsense mutations/frameshift (23.8%) did not use insulin (PZ0.03). No differences were found with regard to mutation types, isoform or domain. We identified several previously undescribed mutations in the cohort including c.-158insGGGTTGG in the promoter region, G31X, E41X, Q130X, L162P, R245I, A269P, S355X, Q398X, Q473X, Q495X, E508X, P588fs-insGCCA and P588fs-delAC. Patients carrying HNF1A polymorphisms were significantly younger at diagnosis than patients with HNF1A mutations (10.9G4.2 vs 14.19G5.8 years; PZ0.027), and all carried I27L, S487N and A98V (nZ3). Conclusion: HNF1A-MODY is the second most frequent MODY diagnosis registered in the DPV database, and previously undescribed HNF1A mutations account for about one-third of HNF1A-MODY cases. Patients with HNF1A polymorphisms documented as HNF1A-MODY were misclassified. They may have autoantibody-negative type 1B or type 2 diabetes or may have other MODY types.

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Section: Discussionmentioning

confidence: 99%

Genetic and clinical characteristics of patients with HNF1A gene variations from the German–Austrian DPV database

Awa

Thon²,

Raile³

et al. 2011

European Journal of Endocrinology

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“…Prevalence of GCK-MODY in Children and Adults With Incidental Hyperglycemia GCK-MODY is a very common cause (23-65%) of incidental hyperglycemia in children, especially when the fasting glucose is persistently above 5.5 mmol/L (29,(40)(41)(42)(43)(44). Awareness of such high GCK-MODY prevalence rates in children with mild fasting hyperglycemia will aid early, correct diagnosis and management.…”

Section: Prevalence Of Gck-mody In Modymentioning

confidence: 99%

Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation

et al. 2015

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Glucokinase–maturity-onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. GCK gene mutations are present in ∼1 in 1,000 of the population, but most are not diagnosed. They are common causes of MODY (10–60%): persistent incidental childhood hyperglycemia (10–60%) and gestational diabetes mellitus (1–2%). GCK-MODY has a unique pathophysiology and clinical characteristics, so it is best considered as a discrete genetic subgroup. People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4–8.3 mmol/L, HbA1c range 5.8–7.6% [40–60 mmol/mol]), which is present from birth and shows slight deterioration with age. Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications. In pregnancy, fetal growth is primarily determined by whether the fetus inherits the GCK gene mutation from their mother. Insulin treatment of the mother is only appropriate when increased fetal abdominal growth on scanning suggests the fetus is unaffected. The impact on outcome of maternal insulin treatment is limited owing to the difficulty in altering maternal glycemia in these patients. Making the diagnosis of GCK-MODY through genetic testing is essential to avoid unnecessary treatment and investigations, especially when patients are misdiagnosed with type 1 or type 2 diabetes.

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“…Maturity-onset of diabetes mellitus of the young (MODY) is another rare form of diabetes mellitus in children that includes several disorders caused by monogenic defects in β-cell function [44] . MODY 2 (defect in glucokinase) and MODY 3 (defect in HNF1α) are the most frequent types of MODY.…”

Section: Differential Diagnosis Of Type 2 Diabetes Mellitus In Childrmentioning

confidence: 99%

Type 2 diabetes mellitus in children and adolescents

Reinehr¹

2013

WJD

295

173

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Phenotypical aspects of maturity‐onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database

Abstract: The prevalence of MODY in children and adolescents in Germany and Austria is lower than that of T2DM in this age group. Dyslipidaemia and hypertension are less frequent in MODY compared with T2DM patients, but do occur.

Cited by 164 publications

References 36 publications

Genetic and clinical characteristics of patients with HNF1A gene variations from the German–Austrian DPV database

Genetic and clinical characteristics of patients with HNF1A gene variations from the German–Austrian DPV database

Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation

Type 2 diabetes mellitus in children and adolescents

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