To the Editor.
We read with great interest the recommendations of Kashtan et al. [1] about the management of Alport syndrome in children. In particular, the protective effect of early treatment with ACE-inhibitors imposes a prompt diagnosis of Alport syndrome that is nowadays still a challenging aspect. As a matter of fact, standard genetic testing with the next generation sequencing approach may miss large gene rearrangements or splice site mutations which represent 5–10% of all pathogenic variants. On the other hand, the case of unfamiliar microhematuria is a frequent finding accounting for around 1% of school-age children. A diagnostic approach such as the one proposed would lead to the execution of a considerable number of kidney biopsies, which is recommended both in isolated microhematuria and in familiarity for hematuria with negative genetic analysis for Alport syndrome. In our opinion, as an intermediate step, a skin biopsy could be a reasonable choice, having small risks related to the procedure compared to kidney biopsy. The X-linked (COL4A5) Alport syndrome remains the most frequent form and, as reported by Wang and colleagues [2], the immunostaining analysis of α5-chain in the epidermal basal membrane from skin fibroblasts gives a mutation detection rate of 83% in males and 93.5% in females heterozygous or with mosaicism for COL4A5 mutation. A pathological skin biopsy could therefore be an indication to perform more specific genetic investigations, as with MLPA technique [3]. The kidney biopsy could therefore be reserved for cases with negative kidney biopsy or with the suspicion of Alport syndrome due to a COL4A3/COL4A4 mutation in which the skin biopsy is not contributive as skin collagen chains are not encoded by these two genes, or again the kidney biopsy could be reserved for cases of COL4A5 mutation not detected by the skin biopsy. Immunostaining for type IV collagen could also be proposed for kidney biopsy showing an absence or an abnormal distribution of the alpha-3,4 or 5(IV) chains of the epidermal basal membrane.
References
Kashtan CE, Gross O (2020) Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol https://doi.org/10.1007/s00467-020-04819-6
Wang F, Zhao D, Ding J, Zhang H, Zhang Y, Yu L, Xiao H, Yao Y, Zhong X, Wang S (2012) Skin biopsy is a practical approach for the clinical diagnosis and molecular genetic analysis of X-linked Alport’s syndrome. J Mol Diagn 14:586–593. https://doi.org/10.1016/j.jmoldx.2012.06.005
Pennesi M, Squillaci D, Diomedi-Camassei F, Pennesi G, Barbi E (2020) A child with familial glomerulonephritis: answers. Pediatr Nephrol 35:1873–1875. https://doi.org/10.1007/s00467-020-04551-1
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Conversano, E., Pennesi, M. Diagnosis of Alport syndrome, is there a role for skin biopsy?. Pediatr Nephrol 36, 1029 (2021). https://doi.org/10.1007/s00467-020-04871-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-020-04871-2