Catastrophic antiphospholipid syndrome accompanied by complement regulatory gene mutation

Area of Science:

• Nephrology
• Rheumatology
• Immunology

Background:

• Antiphospholipid syndrome (APS), especially catastrophic APS (CAPS), is a rare cause of thrombotic microangiopathy (TMA).
• Complement dysregulation significantly worsens CAPS prognosis, leading to severe microvascular thrombosis and multi-organ failure.
• This report details a unique case of CAPS with TMA in a pediatric patient with a genetic complement defect.

Observation:

• A 13-year-old female presented with acute kidney injury, nephrotic proteinuria, hemolytic anemia, and thrombocytopenia, indicative of TMA.
• Initial diagnosis was primary APS; treatment included plasmapheresis, steroids, IVIG, and eculizumab, leading to renal recovery.
• Recurrent TMA symptoms prompted consideration of a CAPS attack, treated with cyclophosphamide and plasmapheresis, resulting in further renal improvement.

Findings:

• The patient was diagnosed with APS and TMA, complicated by complement system dysregulation.
• Genetic analysis revealed a deletion in the Complement Factor H-Related Protein 1 (CFHRP1) gene.
• Despite initial and subsequent aggressive treatments, the patient has residual stage-3 chronic kidney disease.

Implications:

• Complement system dysregulation is a critical factor in severe CAPS-TMA cases.
• Investigating complement pathways and genetic defects is crucial for managing CAPS patients.
• Eculizumab and other complement-targeted therapies should be considered in managing complement-mediated CAPS-TMA.