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Rare genetic variant in the CFB gene presenting as atypical hemolytic uremic syndrome and immune complex diffuse membranoproliferative glomerulonephritis, with crescents, successfully treated with eculizumab

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Abstract

Background

Complement factor B gene (CFB) is an important component of the alternate pathway of complement activation that provides an active subunit that associates with C3b to form the C3 convertase, which is an essential element in complement activation. Among the complement-associated disorders, mutations and pathogenic variants in the CFB gene are relatively rare phenomena. Moreover, mutated CFB affiliation with immune-complex diffuse membranoproliferative glomerulonephritis (IC-MPGN) and atypical hemolytic uremic syndrome (aHUS) are considered a highly rare occurrence.

Case presentation

We describe the clinical presentation, course, and pathological findings in a 7-year-old boy who has confirmed CFB heterozygous variants with pathological features compatible with IC-MPGN. Mutational analysis revealed a heterozygous variant p.Glu566Arg in exon 13 of the CFB gene. The patient did not respond to steroids and mycophenolate mofetil (MMF) therapy but responded clinically and biochemically to eculizumab treatment. This is the first case report of CFB alteration associated with IC-MPGN and aHUS that was successfully treated with eculizumab.

Conclusions

Heterozygous variants in the CFB gene can be pathogenic and associated with IC-MPGN and aHUS. Early diagnosis and prompt management can be essential in preventing end-stage renal disease. Eculizumab may provide an effective modality of treatment.

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Authors’ contributions

• Khalid Alfakeeh: Clinical management and follow-up, data collection and review of the manuscript.

• Mohammed Azar: Clinical management and follow-up, data collection and writing the manuscript.

• Majid Alfadhel: Comment on genetic analysis and review of the manuscript.

• Alsuayri Mansour Abdullah: Data collection.

• Nourah Aludah: Pathological interpretation, image capture, and manuscript review.

• Khaled O. Alsaad: Pathological interpretation, manuscript composition

Author information

Authors and Affiliations

  1. King Saud bin Abdulaziz University for Health Sciences, Nephrology Division, Department of Pediatrics, King Abdulaziz Medical City, MNG-HA, Riyadh, Saudi Arabia

    Khalid Alfakeeh, Mohammed Azar & Alsuayri Mansour Abdullah

  2. Department of Paediatrics, Division of Nephrology, King Abdullah Specialised Children Hospital, Mail Code 1940, King Abdulaziz Medical City, P. O. Box 22490, Riyadh, 11426, Kingdom of Saudi Arabia

    Khalid Alfakeeh

  3. Genetics Division, Department of Pediatrics, King Abdulaziz Medical City, MNG-HA, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

    Majid Alfadhel

  4. Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, MNG-HA, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

    Nourah Aloudah & Khaled O. Alsaad

Authors
  1. Khalid Alfakeeh
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  2. Mohammed Azar
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  3. Majid Alfadhel
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  4. Alsuayri Mansour Abdullah
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  5. Nourah Aloudah
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  6. Khaled O. Alsaad
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Corresponding author

Correspondence to Khalid Alfakeeh.

Ethics declarations

Written informed consent for the publication of this case report and any accompanying images has been obtained from the patient’s mother. A copy of the written consent is available for review by the editor.

Conflict of interest

The authors declare that they have no competing interests.

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Alfakeeh, K., Azar, M., Alfadhel, M. et al. Rare genetic variant in the CFB gene presenting as atypical hemolytic uremic syndrome and immune complex diffuse membranoproliferative glomerulonephritis, with crescents, successfully treated with eculizumab. Pediatr Nephrol 32, 885–891 (2017). https://doi.org/10.1007/s00467-016-3577-0

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  • DOI: https://doi.org/10.1007/s00467-016-3577-0

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