Abstract
Alport syndrome (AS) is the most common form of hereditary nephritis. Females with X-linked AS are heterozygous carriers of the disease mutation. Carrier status in females without a family history has traditionally been diagnosed by kidney biopsy; more recently skin biopsy has been utilized. We report on a 14-year-old girl with long-standing hematuria and intermittent proteinuria who underwent kidney and skin biopsy to establish a definitive diagnosis. Electron microscopy showed extensive thinning of glomerular basement membrane (GBM), with no evidence of lamination. Immunofluorescence staining showed continuous GBM staining for the α3(IV) and α5(IV) collagen chains, whereas the epidermal basement membrane showed discontinuous α5(IV) collagen staining consistent with an X-linked carrier of AS. Few reports have shown discordance between kidney and skin biopsy findings as seen in this case, presumably due to X chromosome lyonization. We therefore suggest that simultaneous kidney and skin biopsies may be more accurate in the assessment of potential female carriers of AS than either kidney biopsy or skin biopsy alone.
References
Kashtan CE, Michael AF (1996) Alport syndrome. Kidney Int 50:1445–1463
Massella L, Muda AO, Faraggiana T, Bette C, Renieri A, Rizzoni G (2003) Epidermal basement membrane α5(IV) expression in females with Alport syndrome and severity of renal disease. Kidney Int 64:1787–1791
Kashtan CE (1998) Alport syndrome and thin glomerular basement membrane disease. J Am Soc Nephrol 9:1736–1750
Rana K, Wang YY, Powell H, Jones C, McCredie D, Buzz M, Udawela M, Savige J (2005) Persistent familial hematuria in children and the locus for thin basement membrane nephropathy. Pediatr Nephrol 20:1729–1737
Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Verellen C, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Krejcova S, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2000) X-linked Alport syndrome: natural history in 195 families and genotype–phenotype correlations in males. J Am Soc Nephrol 11:649–657
Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Dahan K, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2003) X-linked Alport syndrome: natural history and genotype–phenotype correlations in girls and women belonging to 195 families: a “European community Alport syndrome concerted action” study. J Am Soc Nephrol 14:2603–2610
Van der Loop F, Monnens, L, Schroder C, Lemmink H, Breuning M, Timmer, E, Smeets H (1999) Identification of COL4A5 defects in Alport’s syndrome by immunohistochemistry of skin. Kidney Int 55:1217–1224
Ueda T, Nakajima M, Akazawa H, Maruhashi Y, Shimoyama H, Sakagami Y, Takagawa K, Kamitsuji H, Naito I, Sado Y, Yoshioka A (2002) Quantitative analysis of glomerular type IV collagen alpha 3–5 chain expression in children with thin basement membrane disease. Nephron 92:271–278
Liapis H, Gokden N, Hmiel P, Miner JH (2002) Histopathology, ultrastructure, and clinical phenotypes in thin glomerular basement membrane disease variants. Hum Pathol 33:836–845
Pirson Y (1999) Making the diagnosis of Alport’s syndrome. Kidney Int 56:760–775
Gregory MC (2004) Alport syndrome and thin basement membrane nephropathy: unraveling the tangled strands of type IV collagen. Kidney Int 65:1109–1110
Nieuwhof CM, de Heer F, de Leeuw P, van Breda Vriesman PJ (1997) Thin GBM nephropathy: premature glomerular obsolescence is associated with hypertension and late onset renal failure. Kidney Int 11:1256–1260
Nakanishi K, Iijima K, Kuroda N, Inoue Y, Sado Y, Nakamura H, Yoshikawa N (1998) Comparison of α5(IV) collagen chain expression in skin with disease severity in women with X-linked Alport syndrome. J Am Soc Nephrol 9:1433–1440
Gubler MC (2006) Diagnosis of Alport syndrome without biopsy? Pediatr Nephrol DOI https://doi.org/10.1007/s00467-006-0376-z
Slajpah M, Meglic A, Furlan P, Glavac D (2005) The importance of non-invasive genetic analysis in the initial diagnostics of Alport syndrome in young patients. Pediatr Nephrol 20:1260–1264
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hamiwka, L.A., George, D.H., Grisaru, S. et al. Discordance between skin biopsy and kidney biopsy in an X-linked carrier of Alport syndrome. Pediatr Nephrol 22, 1050–1053 (2007). https://doi.org/10.1007/s00467-007-0437-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-007-0437-y