A rare case: childhood-onset C3 glomerulonephritis due to homozygous factor H deficiency
Krisztina Rusai1, Vera Zaller2, Agnes Szilagyi3
1Department of Pediatrics and Adolescent Medicine, Pediatric Nephrology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. krisztina.rusai@meduniwien.ac.at.
Insights
A child with homozygous factor H deficiency presented with C3 glomerulonephritis (C3GN). This rare pediatric case highlights the importance of early detection for factor H deficiency in C3GN.
Area of Science:
- Nephrology
- Immunology
- Genetics
Background:
- C3 glomerulopathy, encompassing dense deposit disease and C3 glomerulonephritis (C3GN), is linked to complement system dysregulation.
- Factor H deficiency can cause C3 glomerulopathy, but complete deficiency is rare, especially in pediatric C3GN cases.
Purpose of the Study:
- To report a rare pediatric case of C3GN associated with complete factor H deficiency.
- To investigate the genetic basis and clinical course of this rare condition.
Main Methods:
- Clinical presentation and laboratory findings of a 10-year-old child with hematuria and proteinuria.
- Kidney biopsy for pathological diagnosis of C3GN.
- Detailed complement analysis, including plasma C3 levels and factor H activity.
- Genetic analysis to identify CFH mutations and CFHR deletions.
Main Results:
- The patient exhibited homozygous factor H deficiency due to a CFH mutation and complete deletion of CFHR-1/-3.
- Kidney biopsy confirmed C3GN with undetectable plasma C3 levels.
- The patient experienced recurrent macro-hematuria but maintained stable renal function over 4 years.
Conclusions:
- Complete factor H deficiency is a rare cause of C3GN, particularly in children.
- This case underscores the need for early diagnosis and highlights a rare clinical manifestation of factor H deficiency.
- Early detection of similar pediatric cases is crucial for timely management.
Abstract:
C3 glomerulopathy is a recently described pathological entity including dense deposit disease and C3 glomerulonephritis (C3GN). In some cases, C3 glomerulopathy is associated with defects or even complete deficiency of factor H. However, complete factor H deficiency among patients with C3GN is rare, and paediatric cases have not yet been described. Here, we report a child with homozygous factor H deficiency who presented with haematuria and minor proteinuria, together with undetectable plasma C3 levels, at the age of 10 years. Kidney biopsy demonstrated C3GN. Detailed complement analysis revealed complete factor H deficiency due to a homozygous CFH mutation. Furthermore, there was a complete deletion of CFHR-1/-3. During follow-up, the patient has had recurrent episodes of macro-haematuria and minor proteinuria, but during 4 years of follow-up, no deterioration of renal function has been observed. Mutations of factor H in C3GN have been described; however, complete CFH deficiency is rare in these patients. Furthermore, clinical presentation usually occurs in adulthood. Therefore, this case presents a rare manifestation of the disease and might contribute to the early detection of similar cases also in childhood.
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