Čes-slov Pediat 2025, 80(5):239-243 | DOI: 10.55095/CSPediatrie2025/038

Atypical HUS with thrombomodulin mutation - clinical course and response to complement inhibition

Ľudmila Podracká^{1, 2}, Darina Buzašiová², Štefan Pavlík³, Kamila Karľová¹

¹ Detská klinika, Lekárska fakulta Univerzity Komenského, Národný ústav detských chorôb, Bratislava

² Detská klinika intenzívnej medicíny a anesteziológie, Lekárska fakulta Univerzity Komenského, Národný ústav detských chorôb, Bratislava

³ Rádiologické oddelenie, Národný ústav detských chorôb, Bratislava

Atypical hemolytic uremic syndrome (aHUS) is a rare disease classified among thrombotic

microangiopathies. It is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury, with dysregulation of the alternative complement pathway being the key pathogenic mechanism. We present the case of a 13-month-old child diagnosed with aHUS, in whom a rare mutation in the thrombomodulin gene (THBD, variant P501L) was identified. This mutation impairs the regulation of

complement activation, thereby contributing to disease development. The clinical course was complicated by severe extra-renal manifestations, including neurological and pulmonary symptoms, which were unresponsive to plasma therapy. Initiation of targeted therapy with eculizumab, later switched to ravulizumab, led to rapid clinical stabilization and sustained remission without relapse of

thrombotic microangiopathy. This case highlights the importance of genetic testing and a personalized therapeutic approach in children with aHUS, especially in the presence of rare genetic variants such as THBD mutations. The authors also address the issue of optimal duration of complement inhibition and the long-term prognosis in this specific patient subgroup.

Keywords: atypical hemolytic uremic syndrome, thrombomodulin, complement, eculizumab

Accepted: September 3, 2025; Published: June 1, 2025  Show citation