A 7-year-old boy has nephrotic syndrome with 4.5 g/day proteinuria, serum albumin 1.8 g/dL, and hypocomplementemia. Renal biopsy shows mesangial and subendothelial deposits on EM, positive C3 and C1q on immunofluorescence, and mesangial hypercellularity with double contours on PAS stain. The child's serum C3 is 40 mg/dL (low) and C4 is normal. Which condition is the most likely underlying diagnosis?

• A Membranoproliferative glomerulonephritis type I (MPGN I) due to immune complex deposition (e.g., hepatitis C-related) ✓
• B C3 glomerulopathy (C3 glomerulonephritis) due to alternative complement pathway dysregulation
• C Dense deposit disease (MPGN type II) due to C3 nephritic factor
• D Lupus nephritis class IV with wire-loop lesions and full-house immunofluorescence

Explanation

MPGN type I (immune complex-mediated) shows mesangial and subendothelial deposits with positive C3 and C1q immunofluorescence, reflecting classical complement pathway activation — hence both C3 and C4 may be low. The tram-track appearance results from mesangial interposition causing double contours of GBM. Dense deposit disease (type II/C3 GN variant) shows isolated C3 with ribbon-like electron-dense intramembranous deposits and C3NeF-driven alternative complement activation (C3 low, C4 normal). The positive C1q here distinguishes immune complex MPGN from pure C3 glomerulopathy.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.