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Neonatal thrombotic microangiopathy secondary to factor I variant with Hirschsprung disease

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Abstract

Neonatal thrombotic microangiopathy (TMA) is a rare and severe disease characterized by a triad of non-immune hemolytic anemia, thrombocytopenia, and organ dysfunction in neonates. We describe herein an early-term infant who underwent hemicolectomy at 4 days of age due to intestinal perforation. Following surgery, the patient had recurrent bouts of vomiting and abdominal distention, together with acute kidney injury, non-immune hemolytic anemia, and severe thrombocytopenia. Low complement levels raised the possibility of complement-mediated neonatal TMA. Finally, genetic tests identified a heterozygous mutation in the complement factor I gene. Anti-C5 monoclonal antibody therapy led to complete cessation of the hematological and renal manifestations, but symptoms of intestinal obstruction recurred. Intestinal biopsy demonstrated aganglionosis, compatible with Hirschsprung disease. This presentation is the first known case of neonatal complement-mediated TMA associated with Hirschsprung disease. Moreover, it highlights the importance of considering a diagnosis of TMA in cases of atypical neonatal infectious presentation.

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Authors and Affiliations

  1. Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Adi Nitzan-Luques, Mordechai Slae & Oded Volovelsky

  2. Department of Pediatric Hematoncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Adi Nitzan-Luques

  3. Pediatric Gastroenterology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Mordechai Slae

  4. Department of Pediatric Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Diaa Zugayar

  5. Renal Section, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA

    Bradley P. Dixon

  6. Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Karen Meir

  7. Pediatric Nephrology Unit, Hadassah-Hebrew University Medical Center, Ein-Kerem Campus, Jerusalem, Israel

    Oded Volovelsky

Authors
  1. Adi Nitzan-Luques
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  2. Mordechai Slae
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  3. Diaa Zugayar
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  4. Bradley P. Dixon
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  5. Karen Meir
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  6. Oded Volovelsky
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Contributions

AN-L and OV drafted the initial manuscript, reviewed, and revised the manuscript. KM analyzed the pathology specimens and critically reviewed and revised the manuscript. MS, DZ and BPD critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

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Correspondence to Oded Volovelsky.

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Nitzan-Luques, A., Slae, M., Zugayar, D. et al. Neonatal thrombotic microangiopathy secondary to factor I variant with Hirschsprung disease. J Nephrol 34, 241–245 (2021). https://doi.org/10.1007/s40620-020-00766-5

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  • DOI: https://doi.org/10.1007/s40620-020-00766-5

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