In 1995, a significant genetic cause of congenital hyperinsulinism (CHI) was identified for the first time by an international working group led by Israeli researches in collaboration with Wolfgang Rabl / Munich Technological University (PMID 7716548): mutations in the sulphonylurea receptor (SUR1). SUR1 has 2 subunits ABCC8 and KCNJ11; mutations were described in both Type 3 diabetes mellitus as well as in CHI. In the case of CHI, subunit  ABCC8 predominates. Subsequently, mutations in the glucokinase gene - the key enzyme in insulin regulation - were described in diazoxide-sensitive patients by the Heidelberg / Düsseldorf und Hamburg University workgroups. (PMID 19053014). A further cause of hyperinsulinism, hyperinsulinism with hyperammonemia (HI/HA),  that traces back to an enzyme defect in the liver´s urea cycle  was described by R. Santer et al. / Hamburg University (PMID 11214910). In 2001, T. Meissner et al. / Düsseldorf University (PMID 1718690) first identified a special form of CHI that manifests itself after physical exertion. Besides the monogenetic forms, CHI can also occur as part of a syndrome (PMID 11529530).

Participants in the Symposium "Nesidioblastose - from molecular pathophysiology to treatment", on November 6, 1998 in Magdeburg: A. Aynsley-Green, K. Mohnike, N. Bannert, C. Nihoul-Fekete, M. Schwanstecher, H. Böhles, H. Klöppel, B. Beinbrech, H. Mau, W. Rabl.

 

CHI´s diagnostic and therapeutic concepts were fundamentally altered at the end of the 1990s through clarification of molecular mechanisms as well as by the differentiation of focal and diffuse forms. To foster collaboration, in 1998 the symposium "Nesidioblastose - from molecular pathophysiology to treatment" was organized with international participation during the annual convention of pediatric endocrinologists (APE) in Magdeburg (see photo). Diagnostic and treatment recommendations were publicized and shortly afterwards a working group was formed in the APS. In 2003, Otonkoski et al. described localization diagnostics for CHI´s focal form using Dopa-PET. Up to this point in time, a focus could only be detected through percutaneous transhepatic pancreatic vein catheterization with insulin assay. This method was limited to experts at the Necker Hospital center in Paris. Children with the focal form of CHI were usually operated on successfully at the same center in Paris. Immediately after the first description in 2003, the L-Dopa-PET (Positron Emissions Tomography) examination was established by W. Mohnike and T. Eberhardt at the Diagnostic-Therapeutic Center (DTZ) at "Frankfurter Tor", Berlin. A consensus conference, organized by K. Mohnike and W. Mohnike in Berlin in 2005 with participants from Europe and the USA, defined parameters for the procedure (PMID 16710094). A further development by the DTZ is represented by the hybrid procedure L-Dopa-PET/CT, which made exact anatomical correlation possible.

In 2009, pediatric surgeon W. Barthlen convoked an international symposium in Greifswald with guests from Paris, London, Brussels and Philadelphia, at which the then-newest diagnostic and treatment advances for hyperinsulinism were presented. First at the Charité and then from 2008 on in Greifswald, W. Barthlen was successful in establishing and developing tissue-saving surgical techniques for focal CHI using laproscopic enucleation (PMID 21325787).

Home    Site Notices    Datenschutz    Sitemap    Print View    Back to top