# Hereditary Angioedema With a Normal Complement Level

## TL;DR

A 2-year-old girl with Down syndrome experienced swelling symptoms typical of hereditary angioedema, but her complement levels were normal, suggesting a rare variant of the condition.

## Contribution

The paper presents a rare case of hereditary angioedema with normal complement levels, expanding the understanding of HAE beyond traditional C1-INH deficiencies.

## Key findings

- A 2-year-old girl with Down syndrome exhibited HAE-like symptoms despite normal complement levels.
- The patient responded positively to C1-INH concentrate and tranexamic acid for symptom relief.
- This case highlights the existence of HAE with normal C1 esterase inhibitor levels, a rare variant of the disease.

## Abstract

Hereditary angioedema (HAE) is an uncommon autosomal dominant disorder, characterized by episodes of oropharyngeal, gastrointestinal, and subcutaneous tissue swelling, often accompanied by discomfort. HAE is primarily associated with mutations in the SERPING1 gene, resulting in insufficient levels or impaired function of C1 esterase inhibitor (C1-INH), an important regulatory protein of the complement system. While types 1 and 2 HAE are well-established entities caused by quantitative and qualitative defects in C1-INH, respectively, the emergence of type 3 HAE, also known as estrogen-dependent HAE, has expanded our understanding of this complex disorder. In this case, a 2-year-old girl with Down syndrome visited the ER after experiencing lip and tongue swelling following the ingestion of ground pepper. Her laboratory results showed that her complement levels were within normal limits despite clinical symptoms. This situation leads to the specific variant of hereditary angioedema called hereditary angioedema with a normal C1 esterase inhibitor (HAE-NI-C1-INH). Although there are currently no approved treatments, positive responses have been seen to her use of C1-INH concentrate and tranexamic acid to alleviate both immediate and delayed symptoms.