X-linked alport syndrome in females

• Published in: Human pathology Vol. 29; no. 4; pp. 404 - 408
• Main Authors: Meleg-Smith, Suzanne, Magliato, Susan, Cheles, Mary, Garola, Robert E, Kashtan, Clifford E
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.1998; Elsevier
• Subjects: Adolescent; Adult; Alport syndrome; Antibodies, Monoclonal; Basement Membrane - metabolism; Basement Membrane - pathology; Basement Membrane - ultrastructure; Biological and medical sciences; Biopsy; Child; Collagen - immunology; Collagen - metabolism; Female; GBM ultrastructure; Genetic Linkage; Glomerulonephritis; Humans; Immunohistochemistry; immunohistochemistry for collagen IV a5; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Kidney Glomerulus - ultrastructure; Male; Medical sciences; Nephritis, Hereditary - genetics; Nephritis, Hereditary - metabolism; Nephritis, Hereditary - pathology; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; renal biopsy; thin basement membrane disease; X Chromosome; AS; TBMD; GBM; Alport syndrome; thin basement membrane disease; renal biopsy; immunohistochemistry for collagen IV a5; GBM ultrastructure; Ig; Human; Glomerulonephritis; Kidney disease; Immunohistochemistry; Binding; Urinary system disease; Electron microscopy; Index (documentation); Kidney; Genetic disease; Pathology; Biopsy; Adult; Female; X-Chromosome; Diagnosis; Immunofluorescence; Child
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/S0046-8177(98)90123-X

Alport syndrome (AS) is in the differential diagnosis of hematuria. Variability in clinical presentation and in the ultrastructural changes of the glomerulus can make the diagnosis of AS a challenge in female patients. The purpose of this report is to present immunostaining for glomerular basement membrane (GBM) expression of α5(IV) as an adjunctive diagnostic method. Renal biopsy specimens from eight female patients with clinical presentation suggestive of AS were studied. The patients were between 7 and 36 years of age; six were between 12 and 15 years. Light microscopy and immunohistochemistry using a monoclonal antibody to α5(IV) were performed. Controls showed a continuous linear pattern along the GBM in normal kidneys and absence in renal biopsy specimens from male X-linked AS patients. To express the variability of the ultrastructural GBM changes among the patients in the series, we developed a semi-quantitative Alport Index, obtained by quantification of severity and extent of ultrastructural GBM changes. With immunohistochemistry, we showed an interrupted, discontinuous linear pattern for α5(IV) in glomeruli from the eight patients in the series, confirming the diagnosis of X-linked AS. The ultrastructutal Alport Index varied between 6 and 47, showing the heterogeneity in the severity of the GBM changes, even among the six patients aged between 12 and 15 years. In three of the eight biopsy specimens, the predominant change was thin GBM, and the Alport Index was below 20. Immunohistochemistry for α5(IV) in renal biopsy specimens can identify female patients heterozygous for X-linked AS. In this series, the method led to the diagnosis of AS in female patients in whom the predominant ultrastructural change was thin basement membrane.