Nephrotic syndrome as the first symptom in Alport syndrome children.

Background: Alport syndrome is a hereditary disorder of type IV collagen characterized by progressive kidney failure. Most childhood cases present with glomerular hematuria and varying degrees of proteinuria.

Materials and methods: We conducted a retrospective study of 7 individuals from 6 families who presented with nephrotic syndrome as the first symptom and were ultimately diagnosed with Alport syndrome and referred to a tertiary pediatric nephrology service between 2016 and 2022.

Results: At first presentation, all patients had hematuria, nephrotic-range proteinuria, and hypoproteinemia. Their mean age at first presentation was 8.9 ± 2.1 years, and kidney biopsies revealed focal segmental glomerulosclerosis in all patients. In 4 cases, steroids and/or immunosuppressants were used inappropriately before the final diagnosis of Alport syndrome. Meanwhile, whole-exome sequencing found 6 different variants, including 4 in COL4A5 and 1 compound heterozygous variant in COL4A3. Among them, 85.7% were severe variants, and 2 variants were not previously reported. The median follow-up duration was 4.4 (IQR, 2.4 - 8.0) years. All patients who received renin-angiotensin-aldosterone system (RAAS) blockers treatment exhibited varying degrees of reduction in proteinuria. However, 2 of them had decline in kidney function and chronic kidney failure, respectively.

Conclusion: Alport syndrome with severe gene variants may present with nephrotic syndrome earlier and more obviously. Attention should be paid to the differential diagnosis of Alport syndrome in patients with nephrotic syndrome and hematuria, particularly to those who respond poorly to steroid therapy or have a family history of hematuria.