Postoperative atypical hemolytic uremic syndrome associated with complement c3 mutation.

Area of Science:

• Nephrology
• Genetics
• Immunology

Background:

• Atypical hemolytic uremic syndrome (aHUS) is a severe condition with a high risk of renal failure and mortality.
• While various triggers are known, aHUS in the postsurgical, nontransplant period is uncommon.
• Typical HUS is often caused by Shiga-like toxins, but aHUS involves complement system dysregulation.

Purpose of the Study:

• To report a rare case of aHUS following cardiovascular surgery in an infant.
• To investigate the underlying genetic cause of aHUS in this patient.
• To highlight a novel mutation in complement component C3 associated with postsurgical aHUS.

Main Methods:

• Clinical case presentation of an 8-month-old boy with postsurgical aHUS.
• Comprehensive laboratory evaluation including complement factor levels, autoantibodies, and ADAMTS-13 activity.
• Genetic analysis including gene sequencing (CFH, CFI, MCP, CFB, THBD) and mutation identification (C3 R425C).

Main Results:

• The patient developed neurological disturbances, acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia post-cardiovascular surgery.
• Standard aHUS workup was negative, ruling out common genetic and antibody-mediated causes.
• A novel mutation (R425C) in complement component C3 was identified as the causative factor, present in asymptomatic relatives.

Conclusions:

• This case demonstrates aHUS can occur after cardiovascular surgery, triggered by a complement C3 mutation.
• Complement C3 mutations represent a potential genetic predisposition to aHUS in specific clinical contexts.
• Early genetic investigation is crucial for understanding aHUS pathogenesis and guiding treatment, even in postsurgical settings.