Abstract / Summary
Abstract Background Renal involvement is a primary determinant of long-term morbidity in glycogen storage disease type Ia (GSD-Ia). It classically presents as non-immune-mediated metabolic nephropathy that slowly advances from asymptomatic glomerular hyperfiltration to focal segmental glomerulosclerosis. The concurrence of an immune-complex glomerulopathy is exceptionally rare. We report the first pediatric case of GSD-Ia complicated by biopsy-proven crescentic IgA nephropathy followed longitudinally over 15 years, shedding light on the diagnostic vigilance and therapeutic adaptations required for superimposed glomerulonephritis. Case presentation: A 15-year-old male with genetically confirmed GSD-Ia had a history of early glomerular hyperfiltration, recurrent nephrolithiasis, and low-grade proteinuria since age 4, remaining clinically stable for over six years on dietary management and angiotensin-converting enzyme inhibitors. At 11 years of age, despite well-controlled metabolic parameters, he abruptly developed nephrotic-range proteinuria (urinary protein-to-creatinine ratio: 7207.5 mg/g Cr; 24-hour urine protein: 4483.8 mg) and hematuria. Given this sharp deviation from typical metabolic nephropathy, a percutaneous renal biopsy was performed. Histopathology revealed chronic tubulointerstitial injury superimposed with crescentic IgA nephropathy featuring cellular and fibrocellular crescents in 7 of 25 glomeruli, strong mesangial IgA deposition, and confluent electron-dense deposits. Induction therapy with oral glucocorticoids and mycophenolate mofetil markedly reduced proteinuria. Due to residual proteinuria, treatment was transitioned to low-dose glucocorticoids combined with tacrolimus, which successfully achieved clinical remission. All immunosuppressants were discontinued by early 2026. At the 15-year follow-up, the patient maintained durable clinical remission with preserved renal function (serum creatinine: 31 µmol/L; urinary protein-to-creatinine ratio: 1051.3 mg/g Cr). Conclusions In patients with GSD-Ia, an abrupt onset of nephrotic-range proteinuria strongly warrants suspicion of superimposed glomerulonephritis rather than intrinsic metabolic nephropathy alone. Prompt renal biopsy is essential to establish an accurate diagnosis. Combining tight metabolic control with targeted calcineurin inhibitor-based immunosuppressive therapy represents an effective dual-track strategy to induce remission and preserve long-term renal function in this complex scenario.