Abstract: PUB278
Cystic Autosomal Dominant Alport Syndrome Masquerading as Polycystic Kidney Disease: Implications for Family Screening andTransplantation
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Wongboonsin, Janewit, Brigham and Women's Hospital, Boston, United States
- Verwillow, Anna, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Savige, Judith A., The University of Melbourne, Melbourne, Victoria, Australia
- Onuchic-Whitford, Ana C., Brigham and Women's Hospital, Boston, Massachusetts, United States
Introduction
Autosomal dominant polycystic kidney disease (ADPKD) and Alport syndrome (AS) are two common monogenic kidney diseases. While their phenotypes are typically distinct, renal cysts may occur in autosomal dominant AS (ADAS), potentially leading to diagnostic confusion. Herein, we describe a family where a prior diagnosis of ADPKD was corrected to ADAS, resulting in implications for family screening and transplantation.
Case Description
A 61-year-old woman presented to our clinic for evaluation as a kidney donor for her brother with ADPKD. She had persistent microscopic hematuria since age 38, negative cystoscopy, normal kidney function and one kidney cyst. Review of her brother’s case revealed that 4 months prior, at age 72 and after years without medical follow-up, he presented to another hospital in renal failure and was started on hemodialysis. He was reportedly diagnosed with ADPKD after an ultrasound demonstrated bilateral kidney cysts and genetic testing found a variant in PKD1. We further evaluated him in our clinic with an MRI that showed small, atrophic kidneys (~8cm) with scattered small (<1.5cm) bilateral cysts. Review of his genetic panel revealed a heterozygous variant of uncertain significance in PKD1 (p.Asn2353Ser) and a heterozygous likely pathogenic variant in COL4A4 (p.Gly481Val – a glycine substitution in Gly-X-Y motif). His sister’s genetic test identified the same 2 variants, and the PKD1 variant was deemed Benign. His diagnosis was thus reverted and both siblings were diagnosed with ADAS. Audiologic screening revealed mild (sister) and moderate (brother) bilateral sensorineural hearing loss. Another sibling tested negative for the COL4A4 variant and became a kidney donor for the brother, who was transplanted successfully.
Discussion
The phenotypic heterogeneity of AS may pose a challenge for its clinical diagnosis. The identification of kidney cysts in AS further complicates this, adding AS as a differential diagnosis for cystic diseases. Thorough family history, review of clinical course, and careful visual inspection of renal imaging become important steps to avoid misdiagnosis. This case also highlights the key role of genetic testing, especially in the setting of atypical imaging, advanced chronic kidney disease, and assessment of family members as kidney donors.