Challenge in pathologic diagnosis of Alport syndrome: evidence from correction of previous misdiagnosis

• Published in: Orphanet journal of rare diseases 2012-12, Vol.7 (1), p.100-100
• Main Authors: Yao, Xiao-Dan, Chen, Xin, Huang, Gao-Yuan, Yu, Yan-Ting, Xu, Shu-Tian, Hu, Yang-Lin, Wang, Qing-Wen, Chen, Hui-Ping, Zeng, Cai-Hong, Ji, Da-Xi, Hu, Wei-Xin, Tang, Zheng, Liu, Zhi-Hong
• Format: Article
• Language: English
• Subjects: Adolescent; Alport syndrome; Case-Control Studies; Collagen; Diagnosis; Diagnostic errors; Disease; Family medical history; Female; Glomerulonephritis - diagnosis; Glomerulosclerosis, Focal Segmental - diagnosis; Humans; Immunohistology; Kidneys; Male; Medical diagnosis; Medical research; Medicine, Experimental; Nephritis, Hereditary - diagnosis; Pathology; Patients; Rare diseases; Renal biopsy; Statistical analysis; Young Adult
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/1750-1172-7-100

Pathologic studies play an important role in evaluating patients with Alport syndrome besides genotyping. Difficulties still exist in diagnosing Alport syndrome (AS), and misdiagnosis is a not-so-rare event, even in adult patient evaluated with renal biopsy. We used nested case-control study to investigate 52 patients previously misdiagnosed and 52 patients initially diagnosed in the China Alport Syndrome Treatments and Outcomes Registry e-system. We found mesangial proliferative glomerulonephritis (MsPGN, 26.9%) and focal and segmental glomerulosclerosis (FSGS, 19.2%) were the most common misdiagnosis. FSGS was the most frequent misdiagnosis in female X-linked AS (fXLAS) patients (34.8%), and MsPGN in male X-linked AS (mXLAS) patients (41.2%). Previous misdiagnosed mXLAS patients (13/17, 76.5%) and autosomal recessive AS (ARAS) patients (8/12, 66.7%) were corrected after a second renal biopsy. While misdiagnosed fXLAS patients (18/23, 78.3%) were corrected after a family member diagnosed (34.8%) or after rechecking electronic microscopy and/or collagen-IV alpha-chains immunofluresence study (COL-IF) (43.5%) during follow-up. With COL-IF as an additional criterion for AS diagnosis, we found that patients with less than 3 criteria reached have increased risk of misdiagnosis (3.29-fold for all misdiagnosed AS patients and 3.90-fold for fXLAS patients). We emphasize timely and careful study of electronic microscopy and COL-IF in pathologic evaluation of AS patients. With renal and/or skin COL-IF as additional criterion, 3 diagnosis criteria reached are the cutoff for diagnosing AS pathologically.