Clinical Report: A Novel Homozygous PRF1 Mutation in Primary HLH

Background

Familial hemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disorder linked to mutations in genes involved in the secretory lysosome-dependent exocytosis pathway. Accurate diagnosis is critical, as the condition can lead to severe complications if not treated promptly. The identification of specific genetic mutations, such as those in the PRF1 gene, is essential for understanding the disease's etiology.

Data Highlights

No numerical data or trial data was provided in the source material.

Key Findings

• A novel homozygous mutation in the PRF1 gene (p.Y296C c.887 A>G) was identified in a 17-year-old male patient.
• The patient presented with symptoms including fever, night sweats, and splenomegaly, alongside significant skeletal changes.
• Laboratory findings included pancytopenia and elevated inflammatory markers, fulfilling HLH-2004 diagnostic criteria.
• Flow cytometry analysis showed absent perforin expression in natural killer cells.
• The patient initially responded well to oral dexamethasone but experienced an HLH flare during steroid taper.

Clinical Implications

Genetic testing may be considered in patients with suspected HLH to identify potential mutations.

Conclusion

This case underscores the significance of recognizing novel genetic mutations in familial HLH and their implications for patient management. Further research is needed to explore the broader phenotypic presentations associated with such mutations.

Related Resources & Content

1. Author(s)/Org, Source, Year -- Title
2. Frontiers in Immunology — Case Report: Genetically primed hyperinflammation: cytomegalovirus-triggered HLH-like syndrome in an adolescent with a gain-of-function STING1 (p.Arg281Trp) variant with novel autosomal dominant inheritance and atypical presentation
3. Frontiers in Pediatrics — A Novel Homozygous ARFGEF2 Splice-Site Variant Causing Periventricular Nodular Heterotopia with Microcephaly
4. Blood Cancer Journal — Characterization of Myeloid Neoplasms with PHF6 Mutations: Genomic Insights and Prognostic Implications from 176 Cases
5. Blood Cancer Journal — Mutational landscape and its clinical significance in paroxysmal nocturnal hemoglobinuria
6. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study
7. Diagnostic guidelines for familial hemophagocytic lymphohistiocytosis revisited - PMC