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Hemolytic uremic syndrome (HUS), characterized by a triad of renal failure, thrombocytopenia, and microangiopathic hemolytic anemia, is a common cause of acute renal failure in children. Differentiation between typical and atypical HUS (aHUS) has significant clinical implications for patient evaluation and management.
Patients negative for Shiga toxin-producing E.coli (STEC) could be associated with an increased risk for complement mutations and poorer prognosis compared with typical HUS.
Therefore, all non-infection-related HUS should undergo detailed genetic testing for pathogenic variants in genes encoding for proteins and regulatory proteins of the complement alternative pathway.
We retrospectively evaluated the clinical outcomes in a cohort of 9 patients aged 8 months to 12 years admitted to the Bambino Gesù Children's Hospital with the diagnosis of HUS from January 2010 to December 2022. These patients were all diarrhea-positive and Shiga toxin-negative (stool culture negative for E. coli and/or negative for Shiga toxin). Treatment choices for HUS patients were guided by the patients’ clinical condition and renal dysfunction.
Detailed genetic tests, including complement factor H (CFH), complement factor B (CFB), complement factor I (CFI), membrane cofactor protein (MCP), complement component 3 (C3), complement factor H related 5 (CFHR5), and thrombomodulin (THBD), were carried out in all patients.
Conclusions
Diarrhea-associated Shiga toxin-negative HUS patients are categorized according to guidelines as having aHUS. Genetic analysis in aHUS patients is important in understanding the underlying pathogenesis. Eculizumab is started empirically before availability of genetic results in view of suspicion aHUS diagnosis. Despite the fact that only one of these patients received eculizumab while the others spontaneously resolved, our study findings show that some atypical patients presenting with diarrhea-associated but STEC negative aHUS have a good prognosis without relapse after nearly 30 months of follow-up. Genetic analysis is crucial in diarrhea-associated STEC negative HUS even if the patient spontaneously resolves, to confirm aHUS diagnosis and to quantify risk of relapse.