Clinical and genetic features of maturity-onset diabetes of the young in pediatric patients: a 12-year monocentric experience

Stefano Passanisi,Bruno Bombaci,Fortunato Lombardo,Giuseppina Salzano

doi:10.1186/s13098-021-00716-6

Abstract

BackgroundA retrospective observational study was conducted to assess the prevalence of maturity onset diabetes of the young (MODY) in a large paediatric population of Southern Italy newly diagnosed with diabetes. Clinical and genetic features of the identified MODY patients were also described.MethodsGenetic testing was performed in children and adolescents newly diagnosed with diabetes who presented autoantibody negativity and fasting C-peptide levels ≥ 0.8 ng/mL. Patients with a low insulin daily dose and optimal glycaemic control after two years from diabetes onset were also investigated for monogenic diabetes, regardless of their autoimmunity status and/or C-peptide levels.ResultsA prevalence of 6.5% of MODY was found. In particular, glucokinase-MODY was the most common type of MODY. The mean age at diagnosis was 9.1 years. Clinical presentation and biochemical data were heterogeneous also among patients belonging to the same MODY group.ConclusionsWe found a relatively high prevalence of MODY among paediatric patients with a new diagnosis of diabetes in comparison to literature data. Our findings highlight that a more detailed clinical evaluation along with easier and less expensive approachability to genetic testing may allow diagnosing an increasing number of MODY cases. A correct, prompt diagnosis is crucial to choose the most appropriate treatment and offer adequate genetic counselling.

Highlights

Maturity onset diabetes of the young (MODY) is a rare condition characterized by autosomal dominant inheritance which is usually diagnosed before 25 years of age [1]
59 (86.8%) were negative for diabetesspecific autoantibodies, 46 (67.6%) had fasting C-peptide level ≥ 0.8 ng/mL, 63 (92.6%) were not on insulin therapy or required insulin daily dose < 0.5 IU/kg along with an optimal glycaemic control (HbA1c < 6.5% or 48 mmol/ mol).Thirty-seven patients (6.5%) were diagnosed as maturity onset diabetes of the young (MODY)
It is well established that patients affected by GCKMODY do not require any pharmacological treatment [15], while patients with hepatocyte nuclear factor 1-alpha (HNF1A) or hepatocyte nuclear factor 4-alpha (HNF4A)-MODY have a good response to sulfonylureas in term of glycaemic control and prevention of micro- and macrovascular complications [24]

Summary

Introduction

Maturity onset diabetes of the young (MODY) is a rare condition characterized by autosomal dominant inheritance which is usually diagnosed before 25 years of age [1]. According to the latest clinical practice recommendations of the American Diabetes Association, MODY belongs to the monogenic diabetes syndromes [2]. Mutations in the hepatocyte nuclear factor 1-alpha (HNF1A), glucokinase (GCK), hepatocyte nuclear factor 4-alpha (HNF4A), and hepatocyte nuclear factor 1-beta (HNF1B) genes are the most frequently identified aetiologies of MODY. Hyperglycaemia is the result of progressive beta-cell function deterioration over time in the absence of clinical signs of insulin resistance. This type of MODY becomes apparent with mild-to-moderate ketoacidosis. HNF4AMODY, called MODY 1, is caused by heterozygous mutations in the HNF4A gene, resulting in a progressive β-cellular dysfunction [21]. Clinical and genetic features of the identified MODY patients were described

Methods

Results

Discussion

Conclusion