De novo X-linked Alport syndrome in a 3-year-old girl

Abstract

Alport syndrome (AS) is an inherited kidney disease that may lead to end-stage renal disease in early adult life. It is a clinically and genetically heterogeneous nephropathy. The possibility of a patient with haematuria or proteinuria being diagnosed as having AS cannot be excluded even if the patient is female or if the family history is unknown. We report a 3-year-old girl with a de novo frameshift mutation, c.3906delA p.(Gly1303Aspfs*17), in the COL4A5 gene. The significance of the electron microscopic study on the glomerular basement membrane must be emphasised because it is the first step towards the diagnosis of AS. Genetic analysis provides the only conclusive diagnosis of AS, by determining the mode of inheritance and prognosis.

Keywords: genetic screening counselling; proteinurea; urinary and genital tract disorders.

Figure 1

Electron microscopy demonstrated segmental thinning of the glomerular basement membrane. Uranyl acetate-lead citrate, magnification ×3000.

Figure 2

Electron microscopy of the kidney biopsy specimen of the patient demonstrating characteristic features of Alport syndrome. The glomerular basement membrane has focal thickening with lamellation, creating a ‘basket weave’ appearance. Uranyl acetate-lead citrate, magnification ×10 000.

Figure 3

Genetic analysis revealed that the patient had a heterozygous frameshift mutation (c.3906delA p.(Gly1303Aspfs*17)) in exon 42, whereas her parents had no mutation.