# Recurrent Atypical Hemolytic-Uremic Syndrome (aHUS) Associated With CD46 Genetic Mutation: A Report of a Rare Case

## TL;DR

A rare case of atypical hemolytic-uremic syndrome caused by a CD46 genetic mutation is reported, emphasizing the need for early diagnosis and treatment.

## Contribution

This paper presents a rare case of aHUS linked to a CD46 mutation, highlighting diagnostic and treatment challenges.

## Key findings

- The patient's condition improved after treatment with eculizumab, a complement-inhibiting monoclonal antibody.
- Diagnosis was made without kidney biopsy due to thrombocytopenia.
- Clinical features and lab results supported aHUS despite nonspecific initial symptoms.

## Abstract

Hemolytic-uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The typical form of HUS is most often associated with Shiga toxin-producing Escherichia coli infection, whereas atypical HUS (aHUS) is a rare variant caused by genetic mutations that disrupt complement regulation. This dysregulation promotes complement deposition on vascular endothelium, leading to microangiopathic hemolysis, platelet consumption, and organ injury, with acute kidney injury being the most common clinical manifestation. We present the case of a 38-year-old male who presented with nonspecific symptoms and was found to have thrombocytopenia, acute kidney injury, and intravascular hemolysis. Laboratory tests showed a negative direct Coombs test, normal ADAMTS13 activity, and a normal bone marrow biopsy. Although a kidney biopsy was considered, it was avoided due to thrombocytopenia, and the diagnosis was made on clinical and laboratory grounds. Plasma exchange and methylprednisolone were initiated but did not improve his platelet count or renal function. He was subsequently started on eculizumab, a monoclonal antibody against complement, which resulted in significant clinical and laboratory improvement. This case report highlights the importance of early diagnosis and appropriate treatment to prevent morbidity and mortality from aHUS. Although it is a rare condition, clinicians should maintain a high index of suspicion for aHUS in patients presenting with features of TMA.