GH-03 Atypical Hemolytic Uremic Syndrome Resulting From a Novel Missense Mutation in Factor H: A Case Report
Start Date
31-3-2023 10:30 AM
End Date
31-3-2023 12:30 PM
Document Type
Poster
Abstract
Atypical Hemolytic Uremic Syndrome (aHUS) is a rare variant of a thrombotic microangiopathy that is characterized by anemia, thrombocytopenia, and renal injury secondary to endothelial cell dysfunction and the formation of microvascular thrombi.
The pathophysiology of aHUS is due either to an inherited or sporadic genetic mutation leading to overactivation of the complement cascade. This is in contrast to the more common Hemolytic Uremic Syndrome (HUS). It likewise produces a similar constellation of clinical findings such as anemia, thrombocytopenia and acute renal injury. However, it most often has a prodrome of a diarrheal illness and is often secondary to exposure from Shiga toxin produced by E. coli O157:H7 or S. dysenteriae. Various mutations have been implicated in the pathogenesis of aHUS including, but not limited to, genes encoding components of the complement cascade: CFB, CFH, CFHR1-5, MCP, CD46, and DGKE. Mutations in some of these genes are also linked to other nephropathic conditions such as C3 glomerulonephritis.
Here we describe a case of aHUS due to a novel heterozygous missense mutation, p.Tyr235His, in exon 5 of CFHR5. This novel mutation may lead to decreased expression of Factor H which normally functions as an inhibitory factor of the complement cascade. Decreased expression of FHR5 in turn could contribute to the overactivation of the complement cascades.
This case highlights the importance of considering aHUS in the differential diagnosis when evaluating a patient with acute renal dysfunction, anemia and thrombocytopenia as well as expands our understanding of the genetic basis for a patient presentation of thrombotic microangiopathy.
GH-03 Atypical Hemolytic Uremic Syndrome Resulting From a Novel Missense Mutation in Factor H: A Case Report
Atypical Hemolytic Uremic Syndrome (aHUS) is a rare variant of a thrombotic microangiopathy that is characterized by anemia, thrombocytopenia, and renal injury secondary to endothelial cell dysfunction and the formation of microvascular thrombi.
The pathophysiology of aHUS is due either to an inherited or sporadic genetic mutation leading to overactivation of the complement cascade. This is in contrast to the more common Hemolytic Uremic Syndrome (HUS). It likewise produces a similar constellation of clinical findings such as anemia, thrombocytopenia and acute renal injury. However, it most often has a prodrome of a diarrheal illness and is often secondary to exposure from Shiga toxin produced by E. coli O157:H7 or S. dysenteriae. Various mutations have been implicated in the pathogenesis of aHUS including, but not limited to, genes encoding components of the complement cascade: CFB, CFH, CFHR1-5, MCP, CD46, and DGKE. Mutations in some of these genes are also linked to other nephropathic conditions such as C3 glomerulonephritis.
Here we describe a case of aHUS due to a novel heterozygous missense mutation, p.Tyr235His, in exon 5 of CFHR5. This novel mutation may lead to decreased expression of Factor H which normally functions as an inhibitory factor of the complement cascade. Decreased expression of FHR5 in turn could contribute to the overactivation of the complement cascades.
This case highlights the importance of considering aHUS in the differential diagnosis when evaluating a patient with acute renal dysfunction, anemia and thrombocytopenia as well as expands our understanding of the genetic basis for a patient presentation of thrombotic microangiopathy.