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Glomerular lesions in patients with late-onset cystinosis with massive proteinuria
Insights
Adolescent cystinosis can present with significant proteinuria and Fanconi syndrome, even with normal kidney function. Renal biopsies revealed typical cystinosis features plus novel C3 and IgM deposits in glomeruli.
Area of Science:
- Nephrology
- Genetics
- Pathology
Background:
- Cystinosis is a rare genetic lysosomal storage disorder.
- Nephropathic cystinosis typically presents in childhood with progressive kidney damage.
- Late-onset or adolescent forms are less common and may have atypical presentations.
Purpose of the Study:
- To describe the clinical and histopathological findings in siblings with adolescent-onset cystinosis.
- To investigate the cause of massive proteinuria and renal dysfunction in these patients.
- To identify any novel pathological features associated with cystinosis.
Main Methods:
- Case series of three siblings diagnosed with adolescent cystinosis.
- Clinical assessment including glomerular filtration rate (GFR) and proteinuria.
- Renal biopsy with histopathological examination and immunofluorescence.
Main Results:
- All three siblings presented with massive proteinuria and Fanconi syndrome, despite preserved or mildly reduced GFR.
- Renal biopsies showed characteristic cystinosis features: polykaryocytosis, glomerular sclerosis, thickened basement membranes, and tubular abnormalities.
- Novel findings included irregular granular deposits of C3 and IgM in the glomeruli, not previously described in cystinosis.
Conclusions:
- Adolescent-onset cystinosis can manifest with significant proteinuria and Fanconi syndrome before substantial GFR decline.
- The presence of C3 and IgM deposits suggests a potential immune-mediated component or complement activation in cystinosis-related glomerular injury.
- These findings expand the understanding of cystinosis pathology and its varied clinical presentations.
Abstract:
3 siblings--2 brothers aged 18 and 13 years, and 1 sister, aged 11 years--with adolescent or late-onset cystinosis presented with massive proteinuria. At the time their glomerular filtration rate was normal or only modestly diminished. Though glomerular injury was evident, renal tubular functional abnormalities were also present. Renal biopsy revealed histopathologic features typical of the nephropathic form of cystinosis with the Fanconi syndrome: polykaryocytosis, varying degrees of glomerular sclerosis, thickening and reduplication of basement membrane, fused foot processes, dilated tubules with altered epithelial cell features, and interstitial fibrosis. Fine granular deposits of C3 and IgM are irregularly distributed in the glomeruli, findings which have not been described in cystinosis. These deposits are possibly immune complexes being deposited in the glomeruli unrelated to the cystine-storage disease or they may represent a localized activation of the complement system induced by the glomerular injury of cystinosis.