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33. Jahrestagung der GPGE
Gastroenterologie A1 Mutations in Plasmalemma Vesicle Associated Protein cause severe syndromic Protein-Losing Enteropathy I. Broekaert1, K. Becker1, 2, I. Gottschalk3, F. Körber4, J. Dötsch1, H. Thiele5, J. Altmüller5, P. Nürnberg5, C. Hünseler1, S. Cirak1, 2 1Department of Pediatrics, University Hospital Cologne; 2Center for Molecular Medicine Cologne, University of Cologne; 3Department of Gynecology, University Hospital Cologne; 4Department of Radiology, University Hospital Cologne; 5Cologne Center for Genomics, University of Cologne
Background: Protein-losing enteropathy (PLE) is characterized by gastrointestinal protein leakage due to loss of mucosal integrity or lymphatic abnormalities. Congenital diarrhea with protein loss needs to be differentiated from congenital diarrheal disorders (CDDs). Primary PLEs are genetically heterogeneous and the underlying genetic defects are currently emerging. Objectives: We report an infant with fatal PLE for whom we aimed to uncover the underlying pathogenic mutation. Methods: We performed whole exome sequencing (WES) for the index patient. Variants were classified based on ACMG guidelines. WES results and our detailed clinical description of the patient were compared to the literature. Results: We discovered a novel homozygous stop mutation (c.988C>T, p.Q330*) in the Plasmalemma Vesicle-Associated Protein (PLVAP) gene in a newborn with fatal PLE, facial dysmorphism, renal, ocular and cardiac anomalies. The Q330* mutation is predicted to result in complete loss of PLVAP protein expression leading to deletion of the diaphragms of endothelial fenestrae, resulting in plasma protein extravasation and PLE. Recently, another single homozygous stop mutation in PLVAP causing lethal PLE in an infant was reported. Conclusions: Our findings ultimately validate PLVAP mutations as cause of syndromic PLE. Prenatal anomalies, severe PLE, and syndromic features may guide the diagnosis of this rare disease.
A.2 Zöliakiediagnose ohne Biopsie – Eine Anwendungsbeobachtung der „ESPGHAN Leitlinie 2012“ A. Leuschner1, K. Werkstetter1, G. Heilig1, C. Walz2, S. Koletzko1 1Abteilung für pädiatrische Gastroenterologie und Hepatologie, Dr. von Hauner‘sches Kinderspital, LMU – Klinikum der Ludwig Maximilians Universität München; 2Pathologisches Institut, LMU – Klinikum der Ludwig Maximilians Universität München
Hintergrund: Die ESPGHAN Leitlinie von 2012 eröffnet die Option einer Zöliakiediagnose ohne Nachweis einer Enteropathie in Duodenalbiopsien, sofern folgende Kriterien erfüllt sind: Gewebstransglutaminase IgA (tTGA-IgA)-Titer über dem Zehnfachen des Normwertes (≥ 10 x ULN), positive Endomysium-Antikörper (EMA) und HLA-DQ2/DQ8-Marker in einer zweiten Blutprobe, mindestens ein Zöliakie-typisches Symptom und Aufklärung über dieses Vorgehen durch einen Kindergastroenterologen. Die ProCeDE-Studie validierte dieses Vorgehen mit einem positiven prä-
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diktiven Wert von > 99 %, die HLA-Analyse erwies sich dabei als verzichtbar (Werkstetter et al. Gastroenterology 2017). W
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