Jeanne Truong1, Georges Deschênes2, Patrice Callard3, Corinne Antignac4, Olivier Niel2,4. 1. Pediatric Nephrology Department, Robert Debré Hospital, 48 boulevard Sérurier, 75019, Paris, France. jeanne.truong09@gmail.com. 2. Pediatric Nephrology Department, Robert Debré Hospital, 48 boulevard Sérurier, 75019, Paris, France. 3. Pathology Department, Tenon Hospital, 4 rue de la Chine, 75020, Paris, France. 4. Molecular Bases of Kidney Development, Inserm U1163 - Sorbonne Paris Cité - Paris Descartes University, 24 boulevard du Montparnasse, 75015, Paris, France.
Abstract
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.
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.
Authors: Jeffrey H Miner; Colin Baigent; Frances Flinter; Oliver Gross; Parminder Judge; Clifford E Kashtan; Sharon Lagas; Judith Savige; Dave Blatt; Jie Ding; Daniel P Gale; Julian P Midgley; Sue Povey; Marco Prunotto; Daniel Renault; Jules Skelding; A Neil Turner; Susie Gear Journal: Kidney Int Date: 2014-07-02 Impact factor: 10.612