Atypical Hemolytic Uremic Syndrome Caused by a Rare Complement Factor B Mutation.

Sai Samyuktha Bandaru

doi:10.7759/cureus.23207

Abstract

Thrombotic microangiopathy (TMA), a rare and diagnostically challenging condition, commonly presents with a triad of thrombocytopenia, hemolytic anemia, and end-organ damage, such as renal failure. Most cases of the hemolytic uremic syndrome (HUS) are mediated by Shiga toxin-producing Escherichia coli, but some cases present as an atypical HUS, which includes thrombotic thrombocytopenic purpura and complement-mediated thrombotic microangiopathy (C-TMA). Although C-TMA occurs because of genetic and acquired mutations in the complement regulatory factors, it is usually hereditary. The currently available treatment options include therapeutic plasma exchange and administration of eculizumab, which is a monoclonal antibody against C5. Here, we report a diagnostically challenging and extremely rare case of a middle-aged Caucasian man who was diagnosed with atypical HUS that was caused by a mutation in complement factor B. This case highlights the importance of not overlooking rare causes of TMAs because the diagnostic evaluation is important for guiding appropriate management and obtaining a favorable prognosis.

Highlights

Thrombotic microangiopathies (TMAs) are usually rare and have multiple etiologies
We present a diagnostically challenging case of complement-mediated thrombotic microangiopathy (C-TMA), which is known as an atypical hemolytic uremic syndrome (HUS)
Because of high suspicion for C-TMA, genetic studies were done and showed heterozygous missense variant mutation in complement factor B (CFB), which increased the formation of C3 convertase

Summary

Introduction

Thrombotic microangiopathies (TMAs) are usually rare and have multiple etiologies. In this report, we present a diagnostically challenging case of complement-mediated thrombotic microangiopathy (C-TMA), which is known as an atypical hemolytic uremic syndrome (HUS). The peripheral smear showed schistocytes, which were suggestive of nonhemolytic anemia consistent with microangiopathic hemolytic anemia (Figure 1) He was thrombocytopenic with platelet counts ranging from 70,000 to 120,000/mL and had elevated creatinine levels ranging from 3 to 6.1 mg/dL. The other workups done to rule out a post-infectious etiology of kidney failure were all negative for antistreptolysin O, anti-nuclear antibody, and anti-glomerular basement membrane These findings suggested disruption in the regulation of the complement pathway and supported a compatible etiology for atypical HUS. Because of high suspicion for C-TMA, genetic studies were done and showed heterozygous missense variant mutation in complement factor B (CFB), which increased the formation of C3 convertase. He was scheduled to receive definitive therapy with eculizumab as an outpatient

Discussion

Conclusions

Disclosures