Zusammenfassung
Die Erforschung seltener Erkrankungen ermöglicht häufig entscheidende Erkenntnisse über die Pathophysiologie des Menschen. Kürzlich haben wir ein neues Krankheitsbild bei Kindern beschrieben, welches mit einem dem Gitelman-Syndrom ähnlichen renalen Salzverlust einhergeht. Ursprünglich wurden die Kinder im Säuglingsalter mit Krampfanfällen auffällig, und später wurden bei Untersuchungen bezüglich einer Entwicklungsverzögerung auch noch Ataxie und Innenohrschwerhörigkeit festgestellt. Diese Kombination von Symptomen war bisher nicht beschrieben worden, und entsprechend benannten wir dieses neu entdeckte Syndrom mit dem Akronym EAST (Epilepsie, Ataxie, Schwerhörigkeit und Tubulopathie). Genetische Untersuchungen an einer konsanguinen Familie mit 4 betroffenen Kindern identifizierten rezessive Mutationen im Kaliumkanal KCNJ10 als Ursache der Erkrankung. Dies unterstreicht die physiologische Relevanz dieses Kanals für Gehirn, Innenohr und Niere. KCNJ10 ist dementsprechend ein potenzieller Angriffspunkt für neue Medikamente, z. B. zur Behandlung von Bluthochdruck oder von Epilepsie.
Abstract
The investigation of rare diseases often reveals important insights into human pathophysiology. Recently, we described a new syndrome in children with renal salt wasting mimicking Gitelman syndrome. The children initially presented in infancy with seizures and investigations into developmental delay later revealed ataxia and sensorineural deafness. This constellation of symptoms was not previously recognized and accordingly we assigned this newly discovered syndrome the acronym EAST (Epilepsy, Ataxia, Sensorineural deafness and Tubulopathy). Investigations in an informative consanguineous family with four affected children revealed the underlying genetic basis as recessive mutations in the potassium channel KCNJ10. This highlights the importance of KCNJ10 in brain and renal physiology and makes it a potential target for new therapies, e.g. for the treatment of hypertension or epilepsy.
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Böckenhauer, D., Stanescu, H., Bandulik, S. et al. EAST-Syndrom. Nephrologe 6, 529–536 (2011). https://doi.org/10.1007/s11560-011-0560-4
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DOI: https://doi.org/10.1007/s11560-011-0560-4