aHUS associated with C3 gene mutation: a case with numerous relapses and favorable 20-year outcome

Siomou, Ekaterini; Gkoutsias, Athanasios; Serbis, Anastasios; Kollios, Konstantinos; Chaliasos, Nikolaos; Frémeaux‐Bacchi, Véronique

doi:10.1007/s00467-015-3267-3

Cited by 9 publications

(7 citation statements)

References 14 publications

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“…Others, like I1157T, associate with aHUS presentations characterized by multiple recurrences and prolonged favorable outcomes. Interestingly, the presence of the MCPggaac aHUS risk polymorphism influences the aHUS presentation in all carriers of C3 mutations ( 10 , 19 – 21 , 23 ), which may be justified because this polymorphism determines reduced expression of MCP on the cellular surface ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

The Relevance of the MCP Risk Polymorphism to the Outcome of aHUS Associated With C3 Mutations. A Case Report

et al. 2020

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Thrombotic microangiopathy (TMA) has different etiological causes, and not all of them are well understood. In atypical hemolytic uremic syndrome (aHUS), the TMA is caused by the complement dysregulation associated with pathogenic mutations in complement components and its regulators. Here, we describe a pediatric patient with aHUS in whom the relatively benign course of the disease confused the initial diagnosis. A previously healthy 8-year-old boy developed jaundice, hematuria, hemolytic anemia, thrombopenia, and mild acute kidney injury (AKI) in the context of a diarrhea without hypertension nor oliguria. Spontaneous and complete recovery was observed from the third day of admission. Persistent low C3 plasma levels after recovery raised the suspicion for aHUS, which prompted clinicians to discard the initial diagnosis of Shigatoxin-associated HUS (STEC-HUS). A thorough genetic and molecular study of the complement revealed the presence of an isolated novel pathogenic C3 mutation. The relatively benign clinical course of the disease as well as the finding of a de novo pathogenic C3 mutation are remarkable aspects of this case. The data are discussed to illustrate the benefits of identifying the TMA etiological factor and the relevant contribution of the MCP aHUS risk polymorphism to the disease severity.

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Section: Discussionmentioning

confidence: 99%

The Relevance of the MCP Risk Polymorphism to the Outcome of aHUS Associated With C3 Mutations. A Case Report

et al. 2020

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“…To the best of our knowledge, only two cases with C3 mutations have been reported, with favorable long term outcome [3,14]. Eculizumab is a monoclonal antibody that inhibits the activation of C5 and the formation of the cell membrane attack complex, which is responsible for the damage produced to native cell structures in aHUS.…”

Section: Discussionmentioning

confidence: 99%

Atypical Hemolytic Uremic Syndrome: Atypical Course and Atypical Mutations Combination

Oc¹

2017

OAJUN

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Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy, associated with dysregulation of the alternative pathway of the complement system, characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. In this report, we discuss the case of a woman with aHUS that carries heterozygous C3, complement factor H and membrane cofactor protein mutations, with an uncommon presentation, clinical course and outcome.

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“…An important finding was that the C3 GoF variants associated with C3G affects regulation by FH and CR1 (fluid phase regulation), while the C3 GoF variants associated with aHUS affect primarily the inactivation of C3b by MCP (cell surface regulation), 54,55 which again illustrates that the pathogenic mechanisms of a particular disease implicates specific aspects of the activation and regulation of the AP (Figure 3). The key contribution of these GoF variants to the disease phenotype is further illustrated by the remarkably reproducible and characteristic presentation of aHUS in carriers of two C3 GoF variants (R161W and I1147T) that are relatively prevalent in Europe and Japan 56–58 . In a different context, the C3‐923delDG variant associated with C3G is also remarkable.…”

Section: Rare Genetic Variants In the Ap And Predisposition To Diseasementioning

confidence: 98%

Genetic variability shapes the alternative pathway complement activity and predisposition to complement‐related diseases

Córdoba

2022

Immunological Reviews

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The complement system is a fundamental part of our innate immunity playing an essential role to fight pathogens and remove immune complexes and cell debris. Complement discriminates between self-components and pathogens, tagging the latter for elimination by phagocytic cells or for direct destruction through cell lysis. Complement activates by three independent pathways, the classical (CP), the lectin (LP), and the alternative (AP). While activation through the CP and LP focuses C3b deposition at the location of the antigens and carbohydrates recognized by complement activating antibodies and lectins, initiation of the AP is based on the spontaneous (or protease-mediated) activation of C3, which ends in the non-specific deposition of C3b in all nearby surfaces. Binding of factor B (FB) to this surface-bound C3b, and activation of the C3bbound FB by factor D (FD), results in the formation of surface-bound unstable protease complexes, named AP C3-convertase (C3bBb)

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aHUS associated with C3 gene mutation: a case with numerous relapses and favorable 20-year outcome

Abstract: We further support that aHUS associated with the p.Ile1157Thr C3 mutation may be highly recurrent, but with recovered renal function. The prevalent p.Ile1157Thr C3 gene mutation has variable disease manifestations and both severe and milder renal phenotypes have been found.

Cited by 9 publications

References 14 publications

The Relevance of the MCP Risk Polymorphism to the Outcome of aHUS Associated With C3 Mutations. A Case Report

The Relevance of the MCP Risk Polymorphism to the Outcome of aHUS Associated With C3 Mutations. A Case Report

Atypical Hemolytic Uremic Syndrome: Atypical Course and Atypical Mutations Combination

Genetic variability shapes the alternative pathway complement activity and predisposition to complement‐related diseases

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