Abstract: TH-PO0848
Early-Onset Steroid-Resistant Nephrotic Syndrome Due to MAGI2 Mutation with Alport Carrier State: A Novel Genotype Association with ESRD
Session Information
- Glomerular Case Reports: Potpourri
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Balestrin, Illan George, Associacao Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
- Vizioli, Luis Henrique, Associacao Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
- Kalil, Milton, Associacao Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
- André, Mauricio Lutzky, Associacao Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
- Stein, Anna Cristina, Associacao Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
- Eick, Renato George, Associacao Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
- Saitovich, David, Associacao Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
- Melere, Camila Mosmann, Associacao Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
- Thomé, Gustavo Gomes, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil
- Da Luz, Lucas G., Associacao Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
Group or Team Name
- Hospital Moinhos de Vento.
Introduction
NS in childhood may have idiopathic or genetic etiologies, the latter being more common in early forms and resistant to immunosuppressive treatment. Mutations in the MAGI2 gene are among the rare monogenic causes associated with SRNS. Reports of association between MAGI2 mutation and Alport disease trait are not found in the current literature, which makes this case unique. Prevalence of monogenic mutations in SRNS, especially in children besides MAGI2 represents less than 2% of cases, according to large cohorts (e.g., NEPTUNE, PodoNet)
Case Description
A 5y old boy with NS since 1 year of age. During the investigation a genetic study was performed that identified a mutation in MAGI2 and COL4A4. The boy was admitted to the ER with progressive drowsiness, sore throat, and bullous skin lesions. Physical examination showed signs of hypovolemia, significant anasarca, and impetigo. He developed a generalized tonic-clonic seizure and admitted ICU and RRT was instituted
Discussion
The simultaneous presence of mutations in MAGI2 and COL4A4 in this case may represent an example of digenic inheritance, a phenomenon increasingly recognized in genetic nephrology
This finding suggests a potential synergistic interaction between podocyte slit diaphragm dysfunction (related to MAGI2) and glomerular basement membrane abnormalities (due to COL4A4 mutation), possibly exacerbating clinical severity and contributing to rapid progression to end-stage renal disease (ESRD)
Electron not yet fully elucidated, it is plausible that filtration slit instability caused by MAGI2 dysfunction may exacerbate the structural fragility of the glomerular basement membrane already compromised by the COL4A4 mutation
To reports have demonstrated the broad phenotypic heterogeneity associated with MAGI2 mutations, ranging from isolated steroid-resistant nephrotic syndrome (SRNS) to multisystemic involvement, neurological manifestations—potentially explaining the occurrence of uremic encephalopathy and seizures in this patient
This are currently no previous reports in the literature documenting this specific genetic combination, raising important questions about potential molecular interactions and an increased risk of progression to ESRD