Atypical hemolytic uremic syndrome in children: Complement mutations and clinical characteristics

Lianne M. Geerdink; Dineke Westra; Joanna A.E. Van Wijk; Eiske M. Dorresteijn; Marc R. Lilien; Jean Claude Davin; Martin Kömhoff; Koen Van Hoeck; Amerins Van Der Vlugt; Lambertus P. Van Den Heuvel; Nicole C.A.J. Van De Kar

doi:10.1007/s00467-012-2131-y

Atypical hemolytic uremic syndrome in children: Complement mutations and clinical characteristics

Lianne M. Geerdink^*
, Dineke Westra
, Joanna A.E. Van Wijk
, Eiske M. Dorresteijn
, Marc R. Lilien
, Jean Claude Davin
, Martin Kömhoff
, Koen Van Hoeck
, Amerins Van Der Vlugt
, Lambertus P. Van Den Heuvel
, Nicole C.A.J. Van De Kar

^*Corresponding author for this work

Pediatrics

Radboud University Medical Center
VU University Medical Center
Utrecht University
University of Amsterdam
Free Universities of Brussels
University Medical Centre Groningen
Antwerp University Hospital
St. Antonius Ziekenhuis
University Hospitals Leuven

Research output: Contribution to journal › Article › Academic › peer-review

134 Citations (Scopus)

15 Downloads (Pure)

Abstract

Background:

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 (αFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (ΔCFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS).

Methods:

Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome.

Results:

In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xαFH, of which five had ΔCFHR1/3); four patients carried combined genetic defects or a mutation, together with αFH. 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.

Conclusions:

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.

Original language	English
Pages (from-to)	1283-1291
Number of pages	9
Journal	Pediatric Nephrology
Volume	27
Issue number	8
DOIs	https://doi.org/10.1007/s00467-012-2131-y
Publication status	Published - Aug 2012

Bibliographical note

Funding Information:
We thank the patients and their parents for participation in this study. This work was partially supported by the Dutch Kidney Foundation (C09.2313, KBSO 07.0004, and KBSO 09.0008).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Cite this

Geerdink, L. M., Westra, D., Van Wijk, J. A. E., Dorresteijn, E. M., Lilien, M. R., Davin, J. C., Kömhoff, M., Van Hoeck, K., Van Der Vlugt, A., Van Den Heuvel, L. P., & Van De Kar, N. C. A. J. (2012). Atypical hemolytic uremic syndrome in children: Complement mutations and clinical characteristics. Pediatric Nephrology, 27(8), 1283-1291. https://doi.org/10.1007/s00467-012-2131-y

@article{93abbedc01914ba083a543014a17eaab,

title = "Atypical hemolytic uremic syndrome in children: Complement mutations and clinical characteristics",

abstract = "Background: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 (αFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (ΔCFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS). Methods:Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome. Results:In 47\% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xαFH, of which five had ΔCFHR1/3); four patients carried combined genetic defects or a mutation, together with αFH. 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. Conclusions: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.",

author = "Geerdink, \{Lianne M.\} and Dineke Westra and \{Van Wijk\}, \{Joanna A.E.\} and Dorresteijn, \{Eiske M.\} and Lilien, \{Marc R.\} and Davin, \{Jean Claude\} and Martin K{\"o}mhoff and \{Van Hoeck\}, Koen and \{Van Der Vlugt\}, Amerins and \{Van Den Heuvel\}, \{Lambertus P.\} and \{Van De Kar\}, \{Nicole C.A.J.\}",

note = "Funding Information: We thank the patients and their parents for participation in this study. This work was partially supported by the Dutch Kidney Foundation (C09.2313, KBSO 07.0004, and KBSO 09.0008). ",

year = "2012",

month = aug,

doi = "10.1007/s00467-012-2131-y",

language = "English",

volume = "27",

pages = "1283--1291",

journal = "Pediatric Nephrology",

issn = "0931-041X",

publisher = "Springer Science+Business Media",

number = "8",

}

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 - Kömhoff, Martin

AU - Van Hoeck, Koen

AU - Van Der Vlugt, Amerins

AU - Van Den Heuvel, Lambertus P.

AU - Van De Kar, Nicole C.A.J.

N1 - Funding Information: We thank the patients and their parents for participation in this study. This work was partially supported by the Dutch Kidney Foundation (C09.2313, KBSO 07.0004, and KBSO 09.0008).

PY - 2012/8

Y1 - 2012/8

N2 - Background: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 (αFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (ΔCFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS). Methods:Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome. Results:In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xαFH, of which five had ΔCFHR1/3); four patients carried combined genetic defects or a mutation, together with αFH. 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. Conclusions: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 - Background: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 (αFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (ΔCFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS). Methods:Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome. Results:In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xαFH, of which five had ΔCFHR1/3); four patients carried combined genetic defects or a mutation, together with αFH. 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. Conclusions: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.

UR - https://www.scopus.com/pages/publications/84863985862

U2 - 10.1007/s00467-012-2131-y

DO - 10.1007/s00467-012-2131-y

M3 - Article

C2 - 22410797

AN - SCOPUS:84863985862

SN - 0931-041X

VL - 27

SP - 1283

EP - 1291

JO - Pediatric Nephrology

JF - Pediatric Nephrology

IS - 8

ER -

Atypical hemolytic uremic syndrome in children: Complement mutations and clinical characteristics

Abstract

Bibliographical note

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