# Pediatric Immunodeficiency Caused by Complement Classical and Alternative Pathway Defects Due to a Homozygous CFI Variant: A Case Report

## TL;DR

A child with a rare CFI gene variant had severe immune issues, showing how this genetic defect affects both complement pathways and leads to infections and autoimmune symptoms.

## Contribution

This case report presents a novel homozygous CFI variant and expands the phenotypic spectrum of CFI deficiency in pediatric patients.

## Key findings

- A homozygous CFI variant (c.848A>G; p.D283G) was identified in a child with severe immunodeficiency.
- The patient showed decreased C3, CFI, and CFH levels and presented with IgA vasculitis and immune complex deposits.
- Symptomatic treatment and peritoneal dialysis improved the child's condition, highlighting the clinical management approach.

## Abstract

Complement factor I (CFI) deficiency is a rare primary immunodeficiency that disrupts the classical and alternative complement pathways, potentially causing severe recurrent infections and autoimmune manifestations in pediatric patients. However, the coexistence of both pathways in a pediatric patient is extremely uncommon. We report a seven-year-old patient with a rare primary immunodeficiency disorder who presented with recurrent middle ear infections, paronychia, gastrointestinal infections, and respiratory infections. Genetic testing revealed a previously unreported homozygous variant in the CFI gene (c.848A>G; p.D283G). Immunological testing showed a decrease in complement C3, CFI, and CFH levels in the patient. Interestingly, the patient presented with IgA vasculitis, with renal pathology showing deposits of immune complexes containing IgA, IgG, IgM, and C1q. By considering the child's condition and genetic test results, the child was treated symptomatically and received regular peritoneal dialysis treatment. Subsequently, the child's condition improved compared to before and was discharged from the hospital. This case highlights the importance of considering CFI deficiency in children with recurrent infections and abnormalities in both the classical and alternative complement pathways. Our findings expand the known phenotypic spectrum of CFI deficiency and contribute to understanding genotype-phenotype correlations in complement disorders.