# Novel Heterozygous Missense Variants in Diacylglycerol Kinase Epsilon and Complement Factor I: Potential Pathogenic Association With Atypical Hemolytic Uremic Syndrome

## TL;DR

A 69-year-old woman developed atypical hemolytic uremic syndrome after surgery, linked to new genetic mutations in DGKE and CFI, and fully recovered with eculizumab treatment.

## Contribution

Identifies novel DGKE and CFI mutations as potential causes of atypical hemolytic uremic syndrome.

## Key findings

- Novel heterozygous missense variants in DGKE and CFI were found in a patient with aHUS.
- Treatment with eculizumab resolved the thrombotic microangiopathy without organ damage.
- The case suggests a possible pathogenic role for these mutations in aHUS.

## Abstract

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA), which copresents with microangiopathic hemolytic anemia, thrombocytopenia, and kidney injury. While typical HUS is normally preceded by infections such as Shiga-toxin-producing Escherichia coli, atypical HUS (aHUS) has a genetic component that leads to dysregulation of the alternative complement pathway. We report a case of a 69-year-old female who developed aHUS after undergoing an elective knee surgery. Genetic testing revealed novel mutations affecting diacylglycerol kinase epsilon (DGKE) protein and complement factor I (CFI) that were not reported before as pathogenic. The patient was treated with eculizumab, leading to the complete resolution of TMA with no lasting organ damage.