Abstract | UNLABELLED: BACKGROUND: OBJECTIVES: We describe the clinical phenotype and nature of complement mutations in a cohort of aHUS patients referred as acute TMAs. PATIENTS/METHODS: Fourteen consecutive aHUS patients were screened for mutations in C3, CD46, CFH, CFI, and CFB, as well as factor H (FH) antibodies. All aHUS patients had ADAMTS-13 activity > 10%. RESULTS: Of 14 aHUS patients, 11 (79%) had platelet counts < 30 × 10(9) /L during the acute phase. Median presenting creatinine level was 295 μmol L(-1) , while five (36%) of 14 presented with a serum creatinine level < 200 μmol L(-1) . Alternative complement pathway mutations were detected in 9 (64%) of 14 patients, including CD46 mutations in five (36%) of 14 patients. Patients were identified with novel mutations in CFB and C3 that have not been previously reported. CONCLUSIONS: We demonstrate that diagnostic differentiation based on platelet count and renal function is insufficient to predict an underlying complement mutation in some aHUS cases. Specifically, we demonstrate a high frequency of functionally significant CD46 mutations which may mimic TTP. ADAMTS-13 activity > 10% in a patient with a TMA should necessitate genetic screening for complement abnormalities.
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Authors | E H Phillips, J P Westwood, V Brocklebank, E K S Wong, J O Tellez, K J Marchbank, S McGuckin, D P Gale, J Connolly, T H J Goodship, D Kavanagh, M A Scully |
Journal | Journal of thrombosis and haemostasis : JTH
(J Thromb Haemost)
Vol. 14
Issue 1
Pg. 175-85
(Jan 2016)
ISSN: 1538-7836 [Electronic] England |
PMID | 26559391
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis. |
Chemical References |
- CD46 protein, human
- Complement C3
- Membrane Cofactor Protein
- Complement Factor B
- ADAMTS13 Protein
- ADAMTS13 protein, human
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Topics |
- ADAMTS13 Protein
(genetics, metabolism)
- Acute Disease
- Adolescent
- Adult
- Aged
- Atypical Hemolytic Uremic Syndrome
(genetics)
- Child, Preschool
- Complement C3
(genetics)
- Complement Factor B
(genetics)
- DNA Mutational Analysis
- Female
- Humans
- Incidence
- Infant
- Kidney Function Tests
- Male
- Membrane Cofactor Protein
(genetics)
- Middle Aged
- Mutation
- Phenotype
- Platelet Count
- Purpura, Thrombotic Thrombocytopenic
(diagnosis, genetics)
- Retrospective Studies
- Thrombotic Microangiopathies
(diagnosis, genetics)
- Young Adult
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