Challenge in Pathologic Diagnosis of Alport Syndrome: Evidence from Correction of Previous Misdiagnosis

Overview

Journal Orphanet J Rare Dis

Publisher Biomed Central

Specialty General Medicine

Date 2012 Dec 25

PMID 23259488

Citations 11

Authors

Xiao-Dan Yao

Xin Chen

Gao-Yuan Huang

Yan-Ting Yu

Shu-Tian Xu

Yang-Lin Hu

Qing-Wen Wang

Hui-Ping Chen

Cai-Hong Zeng

Da-Xi Ji

Wei-Xin Hu

Zheng Tang

Zhi-Hong Liu

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

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