Monogenic Forms of Diabetes Mellitus

  • Zsolt Gaál
  • István BaloghEmail author
Part of the Experientia Supplementum book series (EXS, volume 111)


In addition to the common types of diabetes mellitus, two major monogenic diabetes forms exist. Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic, autosomal dominant diseases. MODY accounts for 1–2% of all diabetes cases, and it is not just underdiagnosed but often misdiagnosed to type 1 or type 2 diabetes. More than a dozen MODY genes have been identified to date, and their molecular classification is of great importance in the correct treatment decision and in the judgment of the prognosis. The most prevalent subtypes are HNF1A, GCK, and HNF4A. Genetic testing for MODY has changed recently due to the technological advancements, as contrary to the sequential testing performed in the past, nowadays all MODY genes can be tested simultaneously by next-generation sequencing. The other major group of monogenic diabetes is neonatal diabetes mellitus which can be transient or permanent, and often the diabetes is a part of a syndrome. It is a severe monogenic disease appearing in the first 6 months of life. The hyperglycemia usually requires insulin. There are two forms, permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). In TNDM, the diabetes usually reverts within several months but might relapse later in life. The incidence of NDM is 1:100,000–1:400,000 live births, and PNDM accounts for half of the cases. Most commonly, neonatal diabetes is caused by mutations in KCNJ11 and ABCC8 genes encoding the ATP-dependent potassium channel of the β cell. Neonatal diabetes has experienced a quick and successful transition into the clinical practice since the discovery of the molecular background. In case of both genetic diabetes groups, recent guidelines recommend genetic testing.


Maturity-onset diabetes of the young Neonatal diabetes mellitus Autosomal dominant 

List of Abbreviations


Carboxyl ester lipase


C-reactive protein




Gestational diabetes mellitus


Hepatocyte nuclear factor 1A


Hepatocyte nuclear factor 1B


Hepatocyte nuclear factor 4A


Maturity-onset diabetes of the young


Neonatal diabetes mellitus


Next-generation sequencing


Online Mendelian Inheritance in Man


Permanent neonatal diabetes mellitus


Transient neonatal diabetes mellitus


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.4th Department of Medicine, Jósa András Teaching HospitalNyíregyházaHungary
  2. 2.Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of MedicineUniversity of DebrecenDebrecenHungary

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