Monitoring complement activity allows a safe reduction in the frequency of ECU administration in aHUS while keeping the disease in remission.

Introduction Atypical hemolytic uremic syndrome (aHUS) is mainly due to complement regulatory gene abnormalities with a dominant pattern but incomplete penetrance. Thus, healthy carriers can be identified in any family of aHUS patients, but it is unpredictable if they will eventually develop aHUS. Methods Patients are screened for 10 complement regulatory gene abnormalities and once a genetic alteration is identified, the search is extended to at-risk family members. The present cohort study includes 257 subjects from 71 families: 99 aHUS patients (71 index cases + 28 affected family members) and 158 healthy relatives with a documented complement gene abnormality. Results Fourteen families (19.7%) experienced multiple cases. Over a cumulative observation period of 7595 person-years, only 28 family members carrying gene mutations experienced aHUS (overall penetrance of 20%), leading to a disease rate of 3.69 events for 1000 person-years. The disease rate was 7.47 per 1000 person-years among siblings, 6.29 among offspring, 2.01 among parents, 1.84 among carriers of variants of uncertain significance, and 4.43 among carriers of causative variants. Conclusions The penetrance of aHUS seems a lot lower than previously reported. Moreover, the disease risk is higher in carriers of causative variants and is not equally distributed among generations: siblings and the offspring of patients have a much greater disease risk than parents. However, risk calculation may depend on variant classification that could change over time.

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Background: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) often caused by complement disregulation for which pregnancy and delivery are common triggers. The disease is associated with a poor prognosis both for the mother and the fetus.Case: A 30-year-old women with a membrane cofactor protein (MCP) gene mutation and two previous aHUS episodes, presented at 23 weeks of pregnancy with no signs of active TMA. Pregnancy proceeded uneventfully and a single dose of Eculizumab was given 24 hours prior to delivery. The patient gave birth to a healthy baby, did not develop TMA and had no side effects. Conclusion:A single prepartum Eculizumab dose may be a cost-effective and safe strategy to face the high risk of relapse in pregnancy-associated aHUS.