Abstract: TH-PO0198
Dual PKD1/ALG5 Variants Presenting as Atypical ADPKD: A Case Report
Session Information
- ADPKD and Cystic Kidney Disease - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Authors
- Greene, Sidney A., University of Kentucky, Lexington, Kentucky, United States
- Ayach, Taha, University of Kentucky, Lexington, Kentucky, United States
Introduction
ADPKD is the most common inherited kidney disorder. While PKD1 and PKD2 mutations account for over 90% of cases, minor genes including ALG5 have been identified as causes of ADPKD-spectrum disease [1]. ALG5 variants impair polycystin-1 maturation and cause atypical ADPKD with non-enlarged cystic kidneys and progressive interstitial fibrosis [2]. We present a case of dual PKD1 non-truncating and ALG5 mutations initially misattributed to NSAID nephropathy.
Case Description
A 65-year-old Caucasian female seen for CKD 3A with Cr 1.2 mg/dL (eGFR of 50 mL/min), bland UA, and no family history CKD. Renal US at an outside facility was normal. CKD attributed to chronic NSAID use. Over two years, eGFR declined to 45 then 40 mL/min with Cr up to 1.5 mg/dL. Repeat imaging (figure 1) revealed normal-sized kidneys with multiple small bilateral simple cysts mostly on the left, raising concern for PKD. Genetic testing identified dual PKD1 non-truncating and ALG5 mutations. TKV 315 mL but given rapid eGFR decline, tolvaptan was initiated per KDIGO guidelines.
Discussion
Case highlights key diagnostic challenges in atypical ADPKD. The absence of family history—seen in up to 15% of cases—combined with reported normal-sized kidneys led to initial attribution of CKD to NSAID nephropathy. The dual PKD1/ALG5 genotype may represent digenic inheritance, where PKD1 non-truncating variant reduces polycystin-1 function while ALG5 dysfunction further impairs its maturation through defective N-glycosylation, compounding reduction below the cystogenic threshold.[2,3] Mayo Imaging Classification should not be applied to patients with minor gene variants; KDIGO recognizes eGFR decline ≥3 mL/min/year as an alternative criterion for tolvaptan initiation. [1] This case underscores the importance of renal genetic testing in unexplained progressive CKD, even without classic ADPKD features, and illustrates how dual mutations in major and minor cystogenes can produce atypical phenotypes with rapid functional decline.
Acknowledgment
1.Autosomal Dominant Polycystic Kidney Disease.Ong ACM, Carriazo S, Ma BM, Torra R, Pei Y. Lancet (London, England). 2026
2.KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of (ADPKD): Executive Summary. Torres VE, Ahn C, Barten TRM, et al. Kidney International. 2025
3.Refining Genotype-Phenotype Correlation in ADPKD. Hwang YH, Conklin J, Chan W, et al. Journal of the American Society of Nephrology : JASN. 2016