Khalid Alfakeeh1,2, Mohammed Azar3, Majid Alfadhel4, Alsuayri Mansour Abdullah3, Nourah Aloudah5, Khaled O Alsaad5. 1. King Saud bin Abdulaziz University for Health Sciences, Nephrology Division, Department of Pediatrics, King Abdulaziz Medical City, MNG-HA, Riyadh, Saudi Arabia. fakeehk@ngha.med.sa. 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. fakeehk@ngha.med.sa. 3. King Saud bin Abdulaziz University for Health Sciences, Nephrology Division, Department of Pediatrics, King Abdulaziz Medical City, MNG-HA, Riyadh, Saudi Arabia. 4. Genetics Division, Department of Pediatrics, King Abdulaziz Medical City, MNG-HA, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. 5. Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, MNG-HA, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
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.
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.
Authors: Jean Hou; Glen S Markowitz; Andrew S Bomback; Gerald B Appel; Leal C Herlitz; M Barry Stokes; Vivette D D'Agati Journal: Kidney Int Date: 2013-09-25 Impact factor: 10.612
Authors: Katherine A Vernon; Elena Goicoechea de Jorge; Angela E Hall; Veronique Fremeaux-Bacchi; Timothy J Aitman; H Terence Cook; Robert Hangartner; Ania Koziell; Matthew C Pickering Journal: Am J Kidney Dis Date: 2012-04-13 Impact factor: 8.860
Authors: Brooke Sadler; Charles G Minard; Gabe Haller; Christina A Gurnett; Sarah H O'Brien; Allison Wheeler; Shilpa Jain; Mutka Sharma; Ayesha Zia; Roshni Kulkarni; Eric Mullins; Margaret V Ragni; Robert Sidonio; Jennifer E Dietrich; Peter A Kouides; Jorge Di Paola; Lakshmi Srivaths Journal: Blood Adv Date: 2022-01-25
Authors: Feng-Mei Wang; Yan Yang; Xiao-Liang Zhang; Yan-Li Wang; Yan Tu; Bi-Cheng Liu; Bin Wang Journal: Front Genet Date: 2021-07-19 Impact factor: 4.599