Macroscopic hematuria with normal renal biopsy-following the chain to the diagnosis: Answers.

BACKGROUND: Alport syndrome (AS) is an inherited glomerular disease associated with hearing and eye defects; its morbidity is a public health issue in developed countries. AS results from mutations in COL4A3, COL4A4, or COL4A5 genes, respectively encoding the alpha-3, alpha-4, and alpha-5 chains of type IV collagen, a major component of the renal glomerular basement membrane (GBM). The diagnosis is usually confirmed by a renal biopsy showing a thinning/thickening of the GBM, with a longitudinal splitting of the lamina densa.

CASE DIAGNOSIS: We report the case of a 10-year-old patient who presented multiple episodes of macroscopic hematuria. On the renal biopsy, the electron microscopy analysis of the GBM was normal, as was the COL4A5 immunofluorescence assay. Genetic analyses showed a homozygous duplication of exons 44 to 47 of the COL4A3 gene, confirming the diagnosis of autosomal recessive AS.

CONCLUSIONS: Our report suggests that in patients with clinical evidence of AS, genetic testing should be performed whenever pathological analysis is not in favor of AS diagnosis. This will ensure that AS patients benefit from an early diagnosis, adequate treatment, and that end-stage renal disease (ESRD) onset is delayed.