Case Report: Pediatric CNS-isolated hemophagocytic lymphohistiocytosis secondary to uniparental disomy of PRF1 mutation

Abstract

Background: Central nervous system-isolated hemophagocytic lymphohistiocytosis (CNS-HLH) is a rare disease caused by mutations in several genes.

Methods: Clinical information was obtained from medical records. Genetic analyses were performed using whole-exome sequencing (WES). NK cell function testing, Granzyme B staining, perforin staining, CD107a mobilization, and soluble CD25 levels were determined.

Results: We report the case of a 5-year-old girl who presented with involuntary movements, an unsteady gait, and a progressively irritable temper. Cranial MRI revealed bilateral multifocal white matter abnormalities. The patient harbored a homozygous missense mutation in the PRF1 gene (NM_001083116.3), c.1349C > T (p.Thr450Met), which is a maternal uniparental disomy. Based on the phenotype and absence of perforin expression, the patient was diagnosed with CNS-HLH.

Conclusion: We report a highly unusual case of CNS-HLH diagnosed by uniparental disomy of a PRF1 mutation. Exome sequencing should be considered in patients with chronic or recurrent brain inflammation who show partial or no response to conventional treatment regimens.

Keywords: PRF1 gene; central nervous system; hemophagocytic lympho-histiocytosis; pediatric; uniparental disomy.

FIGURE 1

Cranial magnetic resonance imaging (MRI). MRI at 1 week of onset (A–D) bilateral basal ganglia, corona radiata, brainstem and anterior-posterior horns of lateral ventricle showed increased signal on T2-FLAIR (A–C) and decreased signal on T1 image (D) MRI at 1 month of onset (E–H) showed progression of the previously described lesions, and new-onset hemorrhage in the left basal ganglia [(E–F) T2-FLAIR; G: T1; H: DWI].