A 15-year experience highlighting the spectrum of Alport kidney disease in the pediatric population and novel genetic variants in COL4A3-5.

Background: Alport kidney disease (AKD) presents one of the most prevalent genetic kidney disorders, characterized by a complex genetic background and diverse clinical manifestations. This study aimed to review the clinical and genetic features of pediatric patients with COL4A3-5 variants and identify novel genetic variants.

Methods: Data were collected retrospectively at a national level from pediatric patients up to 19 years old, who underwent genetic testing between 2008 and 2023. Patients with pathogenic and likely pathogenic COL4A3-5 variants were included. Their clinical, laboratory, and genetic characteristics were presented.

Results: Over 15 years, 85 children and adolescents tested positive for pathogenic or likely pathogenic COL4A3-5 variants. Increasing incidence was noted as genetic testing became more prevalent. One patient (1.2%) progressed to kidney failure and six (7%) had extrarenal involvement. Pathogenic or likely pathogenic variants in COL4A3, COL4A4, and COL4A5 genes were found in 14 (16.4%), 34 (40.0%), and 37 (43.6%) patients, respectively. Patients were diagnosed with autosomal, X-linked, and digenic AKD in 55.2%, 43.6%, and 1.2%, respectively. Eight novel variants were recorded, and their associated phenotype presented.

Conclusions: This study expands the genetic and clinical background of pediatric patients with AKD, presenting on a spectrum from mild hematuria to progressive chronic kidney disease. Genetic confirmation and risk stratification in the pediatric population are critical to ensure timely care and potentially slow down the progression of kidney disease.