Abstract: PUB166
Diagnostic Odyssey of a Case of Autosomal Dominant Tubulointerstitial Kidney Disease MUC-1 (ADTKD MUC-1)
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Guo, Weiwen, Sengkang General Hospital, Singapore, Singapore
- Fong, Jie Ming Nigel, Sengkang General Hospital, Singapore, Singapore
- Teh, Swee Ping, Sengkang General Hospital, Singapore, Singapore
- Loh, Alwin Hwai Liang, Singapore General Hospital Division of Pathology, Singapore, Singapore
- Ng, Jun Li, National University of Singapore, Singapore, Singapore
- Zhang, Yaochun, National University of Singapore, Singapore, Singapore
- Lim, Si Ting, National University of Singapore, Singapore, Singapore
- Koh, Chee Teck, National University Hospital, Singapore, Singapore
- Ng, Kar Hui, National University Hospital, Singapore, Singapore
Introduction
Autosomal dominant tubulointerstitial disease (ADTKD) is characterised by tubulointerstitial damage and fibrosis, bland urinalysis and chronic kidney disease (CKD). We present a young adult, with unexplained CKD and a strong family history, who was diagnosed with ADTKD related to a defect in the MUC-1 gene.
Case Description
A 28-year-old Chinese lady with no medical history was referred for CKD Stage G2A1, detected during a routine screen. She was asymptomatic. Her urinalysis was bland and kidney ultrasound scan was normal. Her father, younger brother, and aunt, uncle and two cousins on paternal side had kidney failure (Fig 1). She progressed rapidly and reached CKD Stage G4A1 over two years and then Stage 5 shortly after. There was no personal or family history of hyperuricemia or gout. Kidney biopsy showed substantial global sclerosis, tubulointerstitial scarring and inflammation, and arteriosclerosis.
Whole exome sequencing (WES) of the proband did not find any pathogenic gene variant. Due to the bland urinalysis, biopsy findings and strong family history, genetic testing for MUC-1 was performed. This revealed a specific Cytosine duplication in the variable number tandem repeat of the MUC-1 gene. This clinched the diagnosis of Mucin-1 kidney disease. Her younger brother also tested positive for the variant while her elder brother had been tested negative. The rest of the family have not been tested. She is currently awaiting kidney transplantation
Discussion
Detailed family history and high clinical suspicion are crucial to diagnosis ADTKD. Kidney biopsy is often non-specific but serves to exclude other causes.
MUC1 testing is not included in WES and specific genetic analysis is required to look for Cytosine duplication in variable number tandem repeat of the MUC1 gene.
Diagnosis of this patient allowed for genetic counselling and cascade testing to identify suitable donors in the family for kidney transplantation.
Family tree