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Adverse Occurrence type:
Time to detection:
Alerting signals, symptoms, evidence of occurrence:
A right liver recipient developed Complement Factor H (CFH) deficiency, following liver transplantation, which was likely to be donor derived. The same recipient also required a kidney transplant six years post initial liver transplant as a result of the initial underlying condition. The CFH deficiency may have resulted in the loss of the subsequent kidney transplant. The transplanted renal graft was lost in 2020 due to Thrombotic Microangiopathy (TMA) which was potentially triggered by CFH alongside a chronic atypical infection. In June 2021, the recipient’s treating team requested the genetic testing of the liver donor. The donor cells were tested for complement related genetic testing. The results showed a likely pathogenic variant in the CFH deficiency gene, which can result in an increased risk of developing atypical haemolytic uremic syndrome (aHUS), which may have triggered the TMA experienced by recipient. There is a risk of reoccurrence for the recipient and there are potential implications for the family of the liver donor.
Demonstration of imputability or root cause:
In June 2021, the recipient’s treating team requested the genetic testing of the liver donor. The donor cells were tested for complement related genetic testing. Test Requested: Massively Parallel Sequencing for Complement dysregulopathy (aHUS, C3GN) panel (11 genes) – from cultured cells of liver donor. Results: CFH (NM 000186.4): c.[350+1G>T];[=] p.[(?)];[=] – Likely pathogenic Interpretation: The DNA from cells of this individual's LIVER donor is heterozygous for the c.350+1G>T variant in the CFH gene.
Suggest new keywords:
Complement Factor H deficiency (CFH), atypical haemolytic uraemic syndrome a(HUS), Thrombotic Microangiopathy (TMA)
Brown et al. (2012) Postpartum aHUS Secondary to a Genetic Abnormality in Factor H Acquired Through Liver Transplantation. 1632-1636
This is a rare interesting case and ready to be published. It will be good if we add the reference as personal communication from Australian Organ and Tissue Authority and if possible an email to communicate. This will provide context to the readers (Manish) - I have e-mailed the request to the OTA team, waiting for their reply (Evi)
Expert comments for publication:
This is an interesting and complex case illustrating the potential of donor derived disease transmission of unusual conditions. CFH deficiency is produced by the liver and has an essential role in the regulation of complement activation. CFH deficiency can cause acquired haemolytic uraemic syndrome (aHUS), a thrombotic microangiopathy. This case illustrates the importance of retention of donor tissue/pathology samples for retrospective testing (even many years later). Although this appears to be a rare case, it is recognised that the rareness may be related to undiagnosed cases.