Background Thrombotic microangiopathy (TMA) defines a group of disorders characterised by microangiopathic haemolytic anaemia, thrombocytopenia, and organ dysfunction, commonly acute kidney injury. Injury of the vascular endothelium is central to the pathogenesis of TMA. We hereby report a case of familial TMA in a Chinese boy with primary CoQ10 deficiency and confirmed COQ6 mutation. Case presentation A Chinese boy presented with steroid-resistant nephrotic syndrome at 8-month-old and went into end-stage kidney disease requiring peritoneal dialysis 7 months later. Whole-exome sequencing revealed compound heterozygous mutations in COQ6 (NM_182476.3) gene c.427G>A p.(Val143Met) and c.1335G>T p.(Arg445Ser), and primary CoQ10 deficiency was subsequently confirmed in skin fibroblasts. At 25 months, he presented with acute onset of respiratory failure and hypertensive encephalopathy, together with the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. TMA was diagnosed and he was initiated on therapeutic plasma exchange and bridged to eculizumab. While on eculizumab for one year with full complement suppression, he had a TMA relapse at four. Eculizumab was taken off at 4-year-old for questionable efficacy, and the patient remained relapse-free for more than 3 years. The older sister of our index patient succumbed to multi-organ failure with histological evidence of TMA when she was four. Retrospective genetic analysis revealed the same compound heterozygous mutation in the COQ6 gene. Discussion This is the first report of familial TMA in a patient with primary CoQ10 deficiency caused by COQ6 genetic variant. The exact mechanism of mitochondrial cytopathy leading to TMA remains unknown. We postulated that mitochondrial dysfunction and severe hypertension contributed to endothelial cell injury, followed by complement activation which contributed to TMA. It should be noted that although C5 inhibitors are recommended as the first line therapy for suspected complement-mediated TMA, patients with C5 inhibitor resistant TMA should be re-evaluated with alternative pathogenic causes.