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HUS with mutations in CFH and STEC infection treated with eculizumab in a 4-year-old girl

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Abstract

Background

Hemolytic uremic syndrome secondary to Shiga-toxin-producing Escherichia coli infection (STEC-HUS) generally shows a favorable outcome. Few cases develop extra-renal complications, since neurological involvement is an important cause of morbidity and mortality. The role of complement in STEC-HUS has been recently highlighted, and the use of eculizumab in severe cases has been communicated. HUS results from environmental and genetic factors, but the simultaneous occurrence of STEC and complement mutations remains undetermined.

Methods

A pediatric case with severe STEC-HUS carrying CFH mutations, with favorable response to eculizumab is analyzed.

Results

STEC-HUS was diagnosed in a 4-year-old girl with classic HUS, including low C3. Peritoneal dialysis was started due to hypertension, oligoanuria, and pleural effusion. She evolved with generalized tonic–clonic seizures and required mechanical ventilation. MRI reported multiple supra- and infratentorial ischemic lesions with laminar/striatal cortical necrosis and leukoencephalopathy. After two eculizumab doses, a significative stabilization in diuresis, blood pressure, creatinine, and C3 was achieved. At the third week, episodes of massive digestive bleeding and a life-threatening condition required a colectomy thus preserving the ileocecal valve. Due to atypical evolution, a genetic study was considered, identifying two heterozygous variants (CFH S1191L/V1197A).

Conclusion

STEC-HUS in patients with a genetic predisposition has been previously reported, but the low frequency of occurrence makes it a rare disease. As in the present case, patients with atypical course might benefit from genetic analysis to evaluate early eculizumab initiation and to better understand its phenotype.

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Acknowledgements

Carla Galvez is a resident fellow of the Pediatric Nephrology Program at the Faculty of Medicine at Universidad de Chile. The genetic CFH/CFI analysis was funded by the Grant FICR19-20 from the Gobierno Regional de la Región de Los Ríos.

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  1. Department of Pediatrics and Child Surgery, Faculty of Medicine, University of Chile, Santiago de Chile, Chile

    Carla Galvez, Paola Krall & Francisco Cano

  2. Institute of Medicine, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile

    Paola Krall & Alejandro Rojas

  3. Department of Pediatric Nephrology, Hepatology and Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Jun Oh

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Galvez, C., Krall, P., Rojas, A. et al. HUS with mutations in CFH and STEC infection treated with eculizumab in a 4-year-old girl. Pediatr Nephrol 38, 1195–1203 (2023). https://doi.org/10.1007/s00467-022-05694-z

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