Atypical Hemolytic Uremic Syndrome (p.Gly1110Ala) with Autoimmune Disease

Area of Science:

• Nephrology
• Genetics
• Immunology

Background:

• Hemolytic uremic syndrome (HUS) is classified as primary (typical or atypical) or secondary, often linked to underlying conditions.
• Atypical HUS (aHUS) typically results from genetic mutations affecting complement regulation, leading to dysregulated complement activation.
• Distinguishing aHUS from secondary HUS is crucial for appropriate treatment, especially with the advent of complement-inhibiting therapies.

Observation:

• A 49-year-old woman presented with aHUS that mimicked secondary HUS with scleroderma.
• Genetic analysis revealed a novel point mutation (p.Gly1110Ala) in the complement factor H gene as the cause of aHUS.
• The patient's presentation complicated diagnosis, initially suggesting secondary HUS.

Findings:

• The identified novel mutation in the complement factor H gene underscores the genetic complexity of aHUS.
• The patient did not have a C5 polymorphism typically targeted by eculizumab.
• Successful treatment was achieved with mycophenolate mofetil, highlighting an alternative therapeutic strategy.

Implications:

• HUS exhibits complex and mixed etiologies, necessitating genetic testing for accurate diagnosis.
• New point mutations in complement genes can cause aHUS, requiring careful genetic evaluation.
• This case emphasizes the importance of considering genetic factors in aHUS and tailoring treatment accordingly, as complement-inhibiting therapy may not always be indicated or effective.