Pediatr Nephrol, 2024

PMID: 39278986

Next-generation sequencing has enabled non-invasive diagnosis of type IV collagen disease beyond the typical presentation of Alport syndrome (AS). A review of clinical and histological records from 2015-2023 identified 43 patients (34 boys) with 39 variants in COL4A5 (n = 27), COL4A4 (n = 7), and COL4A3 (n = 5), with X-linked, autosomal recessive, and autosomal dominant inheritance in 30, 8, and 5 patients, respectively. The median age and eGFR at diagnosis were 10 years and 100.1 ml/min/1.73 m². Fifteen patients initially presented with steroid-resistant nephrotic syndrome, and AS was suspected due to persistent hematuria, low eGFR, characteristic histology, and non-response to immunosuppression. Kidney biopsies revealed focal segmental glomerulosclerosis, minimal change disease, or mesangial proliferative glomerulonephritis. Electron microscopy confirmed glomerular basement membrane changes in 12 cases. Nearly half (48.8%) had sensorineural hearing loss, and 12 patients progressed to chronic kidney disease stages 4-5, with median survival of 15.6 years with eGFR > 30 ml/min/1.73 m². The AS phenotype varies from urinary abnormalities to more severe manifestations, with worse outcomes in boys with X-linked disease.

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