Renal-Limited Thrombotic Microangiopathy in Infants: A Case Series

Rationale & Objective Thrombotic microangiopathy (TMA), an intractable disease, can present in a renal-limited mode. Data on infantile onset renal-limited TMA (RL-TMA) is lacking. This study describes 5 cases of RL-TMA in infants. Study Design Case series Setting & Participants Five infantile-onset RL-TMA patients who were admitted and/or followed up at Nanfang Hospital, Southern Medical University, from January 2024 to June 2025 were collected. Analytical Approach: Clinical data of five patients were collected. Amino acid conservation was analyzed by Clustal Omega, the secondary structure of the mutants was predicted by PolyPhen-2 and PHYRE2, and tertiary structure was predicted by Alphafold3 and ChimeraX. Results All patients presented with acute nephritic syndrome at onset in infantile with hematuria and proteinuria, but without hemolytic anemia or thrombocytopenia. Corticosteroid treatment was attempted in 3 patients, with no response. Renal pathology revealed microthrombi; segmental endothelial cells that swelled with widening of the sub-endothelial gap, and/or mesangiolysis were observed. C3 heterozygous missense variation (c.2184 C>T, p.Cys728X), CD46 homozygous variation c.614A>G (p.Glu205Gly) and CFI heterozygous variation c.610A>G (p.Met204Val) were detected in 3 patients, respectively. Possible activation of alternative complement pathway (AP) was indicated in all 4 tested patients. Complete remission was achieved in 2 patients, and partial responsiveness was observed in another 2 patients who received eculizumab therapy. The patient harbored CFI variation without eculizumab therapy progressed to ESRD at 11 months of age. Limitations Functional verification of genetic variants of C3 , CD46 and CFI in this study were not implemented. AP activation related factors were not checked in patient 5. Conclusions RL-TMA can occur in infancy, which has not been previously reported. Activation of the AP maybe the common cause of infantile onset RL-TMA. Its diagnosis and therapy are challenging. Promising outcomes can be achieved with eculizumab therapy.