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Kidney Week

Abstract: SA-PO686

Disease Risk Among Family Members of Patients with aHUS Carrying Complement Regulatory Gene Abnormality

Session Information

  • Pediatric Glomerular Disease
    November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Ardissino, Gianluigi, Center for HUS Prevention Control and Management, Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
  • Strumbo, Bice, Center for HUS Prevention, Control and Management, Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
  • Capone, Valentina, Center for HUS Prevention Control and Management, Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
  • Cresseri, Donata Carmela, Center for HUS Prevention, Control and Management, Nephrology, Dialysis and Kidney Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
  • Longhi, Selena, Center for HUS Prevention Control and Management, Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
  • Martelli, Laura, Center for HUS Prevention Control and Management, Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
  • Loffredo, Giulia, Center for HUS Prevention, Control and Management, Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
  • Porcaro, Luigi, Center for HUS Prevention, Control and Management, Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
  • Messa, Piergiorgio, Center for HUS Prevention, Control and Management, Nephrology, Dialysis and Kidney Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
  • Tedeschi, Silvana, Center for HUS Prevention, Control and Management, Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico, Milano, Not applicable, Italy
Background

Atypical hemolytic uremic syndrome (aHUS) is a severe thrombotic microangiopathy mainly due to mutations in complement regulatory genes (MCRG) with a dominant pattern (heterozygous can exhibit the disease) but incomplete penetrance thus a number of healthy carriers (HC) can be identified in any family of aHUS patients but it is not clear which, when or why HC will eventually turn into patient. Patients with aHUS referred to our Center are screened for all of the known MCRG and once a genetic abnormality is identified, the search is extended to all the at-risk family members interested in being tested.

Methods

Among all the patients with primary aHUS diagnosed at or referred to our centre, only those with a documented MCRG and their relatives were included: 276 subjects (141 females) with 104 aHUS patients and 172 HC, from 75 families.

Results

Fourteen families(18.7%) experienced multiple cases, 9 subjects had multiple mutations. The mean age at presentation (for patients) or at the time of analysis was 35.2+24.1 years. Over a cumulative observation period of 6408 patient-year, only 29 family members carrying gene mutations experienced aHUS (overall penetrance of 14.4%) leading to a disease rate of 4.5 events for 1000 patient-year. The disease rate was 13.4 among siblings, 10.7 among offsprings and only 3.5 among parents.

Conclusion

In conclusion, the overall penetrance of aHUS seems a lot lower than previously reported, the risk of developing the disease in any given relative carrying MCRG is low but it is not equally distributed among generations: siblings and the offspring of patients have a much greater disease risk compared to parents. This piece of information is very important for genetic counseling and clearly supports the concept of a second hit as a cofactor of aHUS which, most likely, should be searched for in the parent who does not carry the MCRG.

Funding

  • Private Foundation Support