Abstract: PUB169
Dual Molecular Diagnosis: COL4A3 and PKD1
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Hartsell, Sydney Elizabeth, University of Utah Health Hospitals and Clinics, Salt Lake City, Utah, United States
- Ramkumar, Nirupama, University of Utah Health Hospitals and Clinics, Salt Lake City, Utah, United States
- Lloyd, Isaac, Intermountain Health, Salt Lake City, Utah, United States
- Al-Rabadi, Laith, University of Utah Health Hospitals and Clinics, Salt Lake City, Utah, United States
- Gilligan, Sarah, University of Utah Health Hospitals and Clinics, Salt Lake City, Utah, United States
Introduction
Genetic testing is now standard of CKD care. Characterization of dual molecular disease is necessary.
Case Description
A 35-year-old woman established care with a new nephrology practice. She had known CKD G2A1 attributed to ADPKD based on family history and imaging, but additionally with renal biopsy at age 30 demonstrating thin basement membranes with normal texture averaging 190nm (range 160-220nm) (Image). Biopsy was for proteinuria workup (UACR 2.6g) and there was no hematuria or positive serologies. Albuminuria quickly improved after biopsy. Over the next 5 years, despite intermittent RAASi use and avoidance of tolvaptan due to pregnancy desires, her renal function and albuminuria remained normal.
Upon establishing care, genetic testing was sent and revealed dual molecular kidney disease with heterozygous, likely pathogenic mutations in PKD1 (c.8016+1G>A (p.?)) and COL4A3 (c.4265_4273del) p.Ser1422_Gly1424del)). Audiometry identified unilateral sensorineural hearing loss felt to be from previous labyrinthitis, not Alport’s. There was no retinal thinning on optical coherence tomography. She remains off RAASi or tolvaptan while trying to conceive with stable renal function and no hematuria or proteinuria.
Discussion
To our knowledge, only one other case of likely pathogenic dual molecular COL4A3 and PKD1 mutations is reported. There is known propensity toward cyst formation in COL4A3,4,5 mutations of unclear mechanism, potentially from weakened basement membranes. Simultaneously, significant collagen mutations have been reported in 6% of ADPKD patients. Heterozygous COL4A3 mutations have wide phenotypic range and are poorly understood and classified. Increasing use of genetic sequencing will improve understanding of cystic-collagen diseases and their overlap.