Neonataler Diabetes mellitus – diagnostische Herausforderungen und Implikationen für das praktische Management

Zusammenfassung

Der neonatale Diabetes mellitus (NDM) ist eine seltene Erkrankung, der in über 90 % der Fälle eine monogenetische Ursache zugeordnet werden kann. Eine frühzeitige molekulargenetische Diagnostik ist essenziell, um den Krankheitsverlauf antizipieren zu können, spezifische Therapieansätze zu ermöglichen und syndromale Formen mit extrapankreatischen Manifestationen rechtzeitig zu identifizieren. Dieser Artikel gibt einen umfassenden Überblick über die genetische und klinische Heterogenität des NDM, wobei ein besonderer Fokus auf die Pankreasagenesie als eine Ursache dieser Erkrankung gelegt wird. Darüber hinaus werden Herausforderungen und Fallstricke der molekulargenetischen Diagnostik aufgezeigt, die für eine korrekte Diagnosestellung zu berücksichtigen sind. Insbesondere wird diskutiert, welche methodischen Limitationen die klassische NGS-basierte (NGS: Next Generation Sequencing) Panel-Diagnostik aufweist und wie durch den gezielten Einsatz ergänzender Untersuchungsverfahren – etwa die Analyse regulatorischer Sequenzen und epigenetischer Veränderungen – diagnostische Lücken geschlossen werden können. Die praktische Relevanz dieser Aspekte wird anhand eines klinischen Fallbeispiels einer Patientin mit Pankreasagenesie verdeutlicht.

Abstract

Neonatal diabetes mellitus (NDM) is a rare condition that is attributable to a monogenetic cause in more than 90 % of cases. Early molecular genetic testing is essential to predict disease progression, enable targeted treatment approaches, and identify syndromic forms with extrapancreatic manifestations at an early stage. This article provides a detailed overview of the genetic and clinical heterogeneity of NDM, with a particular focus on pancreatic agenesis as one of its causes. In addition, we discuss the challenges and pitfalls of molecular genetic diagnostics that should be considered to ensure accurate diagnosis. The limitations of conventional NGS-based (NGS: next generation sequencing) panel diagnostics are discussed, and ways in which diagnostic gaps might be addressed through additional testing methods, such as the analysis of regulatory sequences and epigenetic modifications. The clinical relevance of these aspects is illustrated by a case study of a patient with pancreatic agenesis.

Schlüsselwörter

monogener Diabetes mellitus - genetische Diagnostik - Pankreasagenesie - transienter Diabetes mellitus

Keywords

Monogenic Diabetes Mellitus - Genetic Diagnostics - Pancreatic Agenesis - Transient Diabetes Mellitus

Publikationsverlauf

Artikel online veröffentlicht:
12. August 2025

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