title: Challenge in pathologic diagnosis of Alport syndrome: evidence from correction of previous misdiagnosis.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. yaoxd@hotmail.com
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Yao
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Gao-Yuan
authors.initials: GY
authors.lastname: Huang
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Yu
authors.forename: Shu-Tian
authors.initials: ST
authors.lastname: Xu
authors.forename: Yang-Lin
authors.initials: YL
authors.lastname: Hu
authors.forename: Qing-Wen
authors.initials: QW
authors.lastname: Wang
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Chen
authors.forename: Cai-Hong
authors.initials: CH
authors.lastname: Zeng
authors.forename: Da-Xi
authors.initials: DX
authors.lastname: Ji
authors.forename: Wei-Xin
authors.initials: WX
authors.lastname: Hu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tang
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D005260:Female; D005921:Glomerulonephritis / Q000175:diagnosis; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis; D006801:Humans; D008297:Male; D009394:Nephritis, Hereditary / Q000175:diagnosis*; D055815:Young Adult