PhD Scientific Days 2019

Budapest, April 25–26, 2019

Clinical and molecular diagnosis in 45 patients referred with HLH

Molnár, Emese

Great Ormond Street Hospital for Children NHS Foundation Trust; Hungarian National Blood Transfusion Service; Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases
Laboratory of Molecular Genetics;

Language of the presentation


Text of the abstract

Familial hemophagocytic lymphohistiocytosis (FLH) is a severe disorder of the immune system characterised by life-threatening inflammation with autosomal recessive inheritance four genes including perforin.

The aim of this retrospective study was to evaluate patients’ perforin expression, molecular
genetic results and clinical presentation in 45 HLH patients.

Clinical data from 45 patients with the clinical suspicion of FHL (median age: 3 years (range: 0-62 years; male to female ratio 1:2) was evaluated and correlated with perforin expression, and with genetic variants in the perforin gene (PRF1). The severity of FHL symptoms was graded by the HLH-2004 protocol. Intracellular perforin expression in CD56+ Natural Killer (NK) cells were screened by flow cytometry.

The frequencies of benign variants in the patient population do not show a significant difference compared to the MAF data (p=non-significant). Patients with damaging PRF1 gene mutations had absent (5 patients) or abnormal (3 patients) perforin expression and met more HLH criteria than patients with benign polymorphism (average: 5.15 versus 3,71, p=0,0071) However, 33% of those patients where benign variants were identified met clinical HLH criteria and had abnormal perforin expression;40% of them had 3 or 4 clinical criteria; in three patients, no HLH phenotype was found, and they had abnormal expression.

The frequency of pathogenic mutations with absent/abnormal expression was significantly higher in this population and was predictable for clinical HLH; however, 33 % of patients without pathogenic PRF1 mutation (only with benign PRF1 variants) also met FHL clinical criteria, and 70 % of them had abnormal perforin expression.

Data of the presenter

Doctoral School: Clinical Medicine
Program: Clinical Haematology (06)
Supervisor: Dr. Andrikovics Hajnalka
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