A personalized approach to the treatment of neonatal diabetes mellitus caused by a KCNJ11 mutation: clinical observations

Neonatal diabetes mellitus (NDM), or diabetes of the newborn, belongs to the group of monogenic forms of the disease and is characterized by marked genetic polymorphism. It is a rare genetically determined disorder with early onset (typically within the first 6 months of life), manifesting as persistent hyperglycemia associated with impaired insulin secretion. To date, more than 30 genes have been identified as being involved in the development of NDM. Among these, mutations in the KCNJ11, ABCC8, and INS genes account for nearly 70% of cases of the permanent form of the disease. Of particular clinical importance are mutations in genes encoding potassium channel function (KCNJ11, ABCC8), as treatment with sulfonylureas, which help normalize channel activity, can restore insulin secretion and enable patients to transition from insulin therapy to oral glucose-lowering agents.

In most patients, such a transition is possible at any age; however, early initiation of sulfonylurea therapy (during the first months of life) is of critical importance, as it may prevent central nervous system damage, which is frequently observed in patients with these mutations.

The identification of genetic mutations has become a key tool for clinicians, enabling precise diagnosis and the selection of the most effective treatment strategies. Timely diagnosis facilitates the initiation of optimal glucose-lowering therapy aimed at achieving target glycemic levels and reducing the risk of complications, particularly those affecting the central nervous system, as well as specific complications of diabetes mellitus.

This article presents two clinical cases of female patients aged 30 and 33 years with NDM, in whom the KCNJ11 p.R201C mutation was identified in adulthood, followed by successful transition from insulin therapy to pathogenetically targeted glucose-lowering treatment.

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