Abstract:

Objective To analyze the clinical phenotypes and mutation types of children with X-linked Alport syndrome （XLAS） with mutations in COL4A5 gene， and to explore the relationship between children with XLAS and nephrotic syndrome nephritic type. Methods Thirty-two children with COL4A5 gene mutations detected by second-generation sequencing and finally diagnosed with Alport syndrome at Guangzhou Red Cross Hospital affiliated with Jinan University and the First People's Hospital of Guangzhou between April 2016 and April 2023 were included， and their clinicopathological features and gene mutation characteristics were retrospectively analyzed. Results The mean age of onset of disease in children with XLAS was （3.68 ± 2.07） years old， the mean age at diagnosis （6.56 ± 2.95） years old， 12 cases （37.5%） started with isolated hematuria， 8 cases （25%） started with hematuria and proteinuria， 12 cases （37.5%） started with nephrotic syndrome nephritic phenotype， and the positive family history of the children was found in 11 cases （34.4%）， ocular lesions were found in 3 cases （9.37%）， ear lesions in 6 cases （18.75%）， and 7 cases （21.87%） were found to have developed chronic kidney disease （CKD） in the later follow-up. 21 children underwent renal tissue puncture biopsy， and electron microscopy showed thinning of the basement membrane （diffuse or segmental） in 13 cases （61.9%）， and uneven thickness of the basement membrane in 8 cases （38.09%）； light microscopy showed thinning of the basement membrane in 13 cases （61.9%）； light microscopy showed thinning of the basement membrane in 8 cases （38.09%）； and light microscopy showed thinning of the basement membrane in 3 cases （11.5%）. （38.09%）； light microscopy： focal segmental glomerulosclerosis （FSGS） in 2 cases （9.52%）， mesangial proliferative glomerulonephritis （Ms PGN） in 11 cases （52.38%）， and minimal change disease （MCD） in 8 cases （38.09%）. The type of mutation was categorized as missense mutation in 12 cases （37.5%）， shear site mutation in 9 cases （28.12%）， nonsense mutation in 6 cases （18.75%）， deletion mutation in 3 cases （9.37%）， and code shift mutation in 2 cases （6.25%）. Genetic mutations were present in 22 cases （68.75%）； spontaneous mutations were present in 10 cases （27.02%）. Conclusions Children with XLAS have atypical clinical manifestations and pathologic features in the early stage of the disease， and the progress is slow， and some of them are easy to be misdiagnosed as nephrotic syndrome nephritis type in the early stage， so it is important to improve the genetic test for this disease as early as possible， and to make reasonable drug choices to predict the prognosis scientifically.

Key words: COL4A5, Alport syndrome, nephrotic syndrome nephritic type, clinical