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Abstract: SA-PO356

Identification of X-Linked Alport Syndrome by Genetic Testing in a Girl Who Had Remained Undiagnosed After Two Kidney Biopsies Within a 10-Year Period

Session Information

Category: Trainee Case Report

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Fujii, Yuko, Osaka Medical College, Takatsuki, OSAKA-FU, Japan
  • Matsumura, Hideki, Osaka Medical College, Takatsuki, OSAKA-FU, Japan
  • Yamazaki, Satoshi, Osaka Medical College, Takatsuki, OSAKA-FU, Japan
  • Tanaka, Tomoko, Osaka Medical College, Takatsuki, OSAKA-FU, Japan
  • Shirasu, Akihiko, Osaka Medical College, Takatsuki, OSAKA-FU, Japan
  • Nakakura, Hyogo, Osaka Medical College, Takatsuki, OSAKA-FU, Japan
  • Nozu, Kandai, Kobe University, Kobe, Japan
  • Iijima, Kazumoto, Dept. of Pediatrics, Kobe Univ. Graduate School of Medicine, Kobe, Japan
  • Ashida, Akira, Osaka Medical College, Takatsuki, OSAKA-FU, Japan
Introduction

Girls with X-linked Alport syndrome (XLAS) are reported to show slower disease progression than boy patients, and most of them are asymptomatic carriers. Previous reports suggest that proteinuria begins at a median age of 7 years, finally resulting in end-stage kidney disease at a median age of 65 years. However, it is well known that the rate of disease progression in girls with XLAS cannot be predicted accurately, and that the clinical phenotype shows considerable variation, even among affected girls in the same family.

Case Description

We describe a girl with XLAS who showed hematuria and proteinuria in a kindergarten urine test at the age of one year, and who was followed up regularly thereafter. Her father had undergone kidney transplantation due to an unknown primary kidney disease when he was in high school. At the age of 7 years, the patient underwent initial kidney biopsy. Light microscopy revealed mesangial proliferation but an immunofluorescence study revealed no IgA deposition, and electron microscopy demonstrated no basement membrane abnormalities. The patient was therefore diagnosed as having non-IgA mesangial proliferative glomerulonephritis. As her proteinuria persisted at about urine protein-creatinine ratio; 0.5 g/gCr, therapy with a cocktail of prednisolone, mizoribine, warfarin, and dipyridamole was started at the age of 8 years, and this led to a gradual decrease of the proteinuria to 0.2 g/gCr. However, from the age of 13 years, the proteinuria and creatinine increased gradually to 1.0 g/gCr and 1.0 mg/dL, respectively, so we performed a second kidney biopsy which yielded results similar to the first one. Finally, at the age of 17 years, we conducted genetic testing of both the patient and her parents. This revealed that the patient had a heterozygous missense mutation in intron 7 of the COL4A5 gene, and that her father was homozygous for the mutation.

Discussion

This girl showed relatively rapid progression of XLAS. Most girls with XLAS have no problem with ocular lesions or hearing, and those with decreased kidney function are very rare. Therefore, even today many clinical issues remain unclear, and diagnosis of XLAS in girls is sometimes very difficult without genetic testing.