Genetic aspects of obstetric atypical hemolytic uremic syndrome


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Abstract

Atypical hemolytic uremic syndrome (aHUS) in 12-31% of cases is associated with pregnancy or childbirth. According to the contemporary concept of aHUS, the genetic defect in the complement system only predisposes to developing aHUS. Any pregnancy complications in women with genetic defects of the complement system may become an additional complement-activating factor apart from the pregnancy, starting the development of aHUS. Aim. To investigate the clinical features of obstetric aHUS compared with the genetic profile of the complement system. Material and methods. The study included 5 patients aged 20 to 33 years (28.2±4.8 years) with obstetric aHUS, treated with Eculizumab. All patients underwent genetic testing. Results. In all patients, aHUS was preceded by various combinations of additional complement-activating conditions: diarrhea, food poisoning, preeclampsia, manual removal of the placenta, bleeding, surgery, sepsis. In all patients, thrombotic microangiopathy was systematic, involving not only the kidneys, but also the liver, lungs and central nervous system. Mutations associated with aHUS (CFH and CFI), were found only in two patients. Polymorphisms of complement system genes were identified in all women, including two patients who had mutations pathognomonic for aHUS. At the same time there was the concordance of the same polymorphisms: FACTOR H (CFH C.2016A>G AND CFH C.2808G>T, CFH C.1419G>A) and C3 (C3 C.941C>T; C3 C.304C>G). Conclusion. aHUS may be caused by many genetic abnormalities, although not all of them are known today. In obstetric aHUS as in aHUS generally, mutations in complement genes only predispose to the disease. This genetic predisposition may be activated by any additional complement-activating condition, including a variety of pregnancy and delivery complications and genetic blood clotting disorders.

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References

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