TY - JOUR
T1 - Atypical hemolytic uremic syndrome in children
T2 - complement mutations and clinical characteristics
AU - Geerdink, Lianne M.
AU - Westra, Dineke
AU - van Wijk, Joanna A. E.
AU - Dorresteijn, Eiske M.
AU - Lilien, Marc R.
AU - Davin, Jean-Claude
AU - Komhoff, Martin
AU - Van Hoeck, Koen
AU - van der Vlugt, Amerins
AU - van den Heuvel, Lambertus P.
AU - van de Kar, Nicole C. A. J.
PY - 2012/8
Y1 - 2012/8
N2 - Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (alpha FH) with or without a homozygous deletion in CFH-related protein 1 and 3 (a dagger CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS).Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome.In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6x alpha FH, of which five had a dagger CFHR1/3); four patients carried combined genetic defects or a mutation, together with alpha FH. In the majority (87%), disease onset was preceeded by a triggering event; in 25% of cases diarrhea was the presenting symptom. More than 50% had normal serum C3 levels at presentation. Relapses were seen in half of the patients, and there was renal graft failure in all except one case following transplant.Performing adequate DNA analysis is essential for treatment and positive outcome in children with aHUS. The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options.
AB - Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (alpha FH) with or without a homozygous deletion in CFH-related protein 1 and 3 (a dagger CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS).Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome.In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6x alpha FH, of which five had a dagger CFHR1/3); four patients carried combined genetic defects or a mutation, together with alpha FH. In the majority (87%), disease onset was preceeded by a triggering event; in 25% of cases diarrhea was the presenting symptom. More than 50% had normal serum C3 levels at presentation. Relapses were seen in half of the patients, and there was renal graft failure in all except one case following transplant.Performing adequate DNA analysis is essential for treatment and positive outcome in children with aHUS. The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options.
KW - Atypical HUS
KW - Complement regulation
KW - Plasma therapy
KW - Dialysis
KW - Transplantation
KW - Clinical outcome
KW - FACTOR-H-AUTOANTIBODIES
KW - COFACTOR PROTEIN CD46
KW - OF-FUNCTION MUTATIONS
KW - THROMBOTIC MICROANGIOPATHY
KW - FACTOR-B
KW - FACTOR-I
KW - PREDISPOSE
KW - IMPACT
KW - TRANSPLANTATION
KW - DEFICIENCY
U2 - 10.1007/s00467-012-2131-y
DO - 10.1007/s00467-012-2131-y
M3 - Article
VL - 27
SP - 1283
EP - 1291
JO - Pediatric Nephrology
JF - Pediatric Nephrology
SN - 0931-041X
IS - 8
ER -