A genetic storm an adult: unmasking familial HLH — a rare presentation

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life‑threatening hyperinflammatory syndrome, with familial (primary) HLH typically manifesting in infancy. Adult‑onset familial HLH—particularly due to mutations in PRF1 (type 2)—is exceedingly rare. We report a 26‑year‑old veterinary student who presented with fever, jaundice, pancytopenia, hepatosplenomegaly, and shock. Investigations confirmed hyperferritinemia, hypofibrinogenemia, hypertri-glyceridemia, hemophagocytosis on bone marrow, and EBV detection on PCR. Genetic testing revealed a pathogenic autosomal recessive PRF1 mutation, confirming familial HLH type 2. Despite initiation of high‑dose steroids, IVIG, and supportive care, disease activity persisted, and the patient subsequently left against medical advice, before the proposed treatment could be initiated. This case underscores the importance of considering primary HLH even in adults, and the role of genetic testing to guide diagnosis and management.