# Clinical Presentations, Diagnosis, and Genetic Features of Hemophagocytic Lymphohistiocytosis: A Single Institutional Experience With the Saudi Population

## TL;DR

This study explores the clinical features and genetic mutations of hemophagocytic lymphohistiocytosis in Saudi Arabia, highlighting common mutations and their geographic and tribal associations.

## Contribution

The study identifies STXBP2 as the most common mutation in Saudi HLH patients and reveals geographic and tribal associations with specific genetic variants.

## Key findings

- 48 out of 59 patients had 15 pathogenic mutations of primary HLH.
- The c.1430C>T variant in STXBP2 was the most common mutation (42.4% of patients).
- RAB27A mutations were associated with older age of presentation compared to PRF1 mutations.

## Abstract

Background

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal condition caused by high immune activation. The present study aimed to identify the clinical manifestations, geographic distribution, and associated pathogenic genetic mutations of HLH in Saudi Arabia.

Method

A retrospective cross-sectional study was conducted at King Fahad Medical City (KFMC), with a total of 59 patients diagnosed with HLH in the period between 2006 and 2018. All genetic results and clinical and biochemical data were retrieved and statistically analyzed using IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States).

Results

The results revealed that 48 patients (81.4%) had 15 pathogenic mutations of primary HLH whereas 8 (13.6%) patients had no genetic mutation. The most common variant mutation identified was c.1430C>T of the STXBP2 gene (42.4% of total patients), followed by c.1122G>A of the PRF1 gene (10.2% of patients), which demonstrated a distinctive geographic and tribal association. Patients with RAB27A mutation tend to present at an older age than the others with a median age of presentation of 5.5 months vs 2 months for patients with PRF1 mutations. No significant differences in clinical features were observed among the various groups.

Conclusion

This study highlights the incidence of genetic mutations among the Saudi population with HLH. The STXBP2 is the most common mutation followed by PRF1 mutations, many mutation variants are associated with a distinctive tribal and geographic association.