Phenotype of autosomal dominant Alport syndrome with a likely pathogenic heterozygous variant in the COL4A3 gene (Gly366Arg) and incidental teratozoospermia: A case report

Autosomal dominant Alport syndrome (ADAS) is the least common form of Alport syndrome, the second most common monogenic cause of chronic kidney disease after autosomal dominant polycystic kidney disease. We report a 14-year follow-up of a patient with ADAS carrying a likely pathogenic heterozygous variant in COL4A3 (Gly366Arg substitution). The disease initially presented with microhematuria and no renal impairment on analysis or ultrasound. The patient progressively developed bilateral renal cysts and renal failure -a classic renal pattern of the syndrome- and bilateral hearing loss. Incidentally, infertility study (had not children) showed teratozoospermia and elevated levels of luteinizing hormone and progesterone, hormones associated with spermatogenesis. Long-term follow-up of rare variants of Alport syndrome helps refine genotype-phenotype correlations and disease progression. The incidental finding of teratozoospermia raises the possibility of an etiological association, that warrants further investigation as a3(IV) collagen chains involved in spermatogenesis are present in seminiferous tubules.