Abstract: FR-PO0129
Dual Diagnosis of Gitelman Syndrome and Alport Syndrome: A Novel Case of Digenic Kidney Disease
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Zubair, Maha, LSU Health Shreveport, Shreveport, Louisiana, United States
- Ahmed, Mohamed Mohyedin, LSU Health Shreveport, Shreveport, Louisiana, United States
- Morisetti, Phani Purushotham, LSU Health Shreveport, Shreveport, Louisiana, United States
- Abreo, Kenneth D., LSU Health Shreveport, Shreveport, Louisiana, United States
Introduction
Gitelman syndrome (GS) and Alport syndrome (AS) are distinct inherited kidney disorders that have not been previously documented to co-occur. We report a case of dual genetic diagnosis discovered through comprehensive genetic testing in a patient with long-standing GS who developed new-onset proteinuria.
Case Description
A 40-year-old woman presented to re-establish care after relocating states. She was diagnosed with GS at age 13 following evaluation for muscle weakness and hypokalemia. Genetic testing was performed to confirm whether she had Bartter or Gitelman syndrome which revealed compound heterozygous pathogenic variants in SLC12A3 (c.482G>A and c.644T>C), confirming GS, and an incidental heterozygous likely pathogenic variant in COL4A3 (c.4982G>A), consistent with autosomal dominant AS.
Laboratory evaluation demonstrated persistent hypokalemia (3.1-3.4 mmol/L), normal serum creatinine (0.8 mg/dL). Notably, urinalysis from 2015 showed no proteinuria, but repeat testing in 2026 revealed urine albumin-to-creatinine ratio of 254 mg/g and urine protein-to-creatinine ratio of 0.43 g/g. The patient had no family history of kidney disease, hearing loss, or ocular abnormalities. The genes SLC12A3 (16q13) and COL4A3 (2q36-37) are located on different chromosomes, representing true digenic inheritance rather than contiguous gene deletion.
Discussion
This case illustrates the diagnostic complexity of dual genetic kidney diseases. The development of proteinuria at age 40 is most likely attributable to the heterozygous COL4A3 mutation, as recent evidence demonstrates that 14-30% of COL4A3 heterozygotes develop kidney impairment and proteinuria. While GS can cause proteinuria in 28% of adult patients, it typically presents with glomerulopathy secondary to chronic RAAS activation rather than new-onset proteinuria after decades of stable disease. The patient's dual diagnosis necessitates monitoring for progressive chronic kidney disease while continuing management of electrolyte abnormalities from GS. This case underscores the value of genetic testing in patients with inherited kidney disease as dual genetic diagnoses occur in at least 5% of genetically diagnosed kidney disease patients.