Familial hemophagocytic lymphohistiocytosis type 5 in a Chinese Tibetan patient caused by a novel compound heterozygous mutation in STXBP2

RATIONALE: Familial hemophagocytic lymphohistiocytosis (FHL) is a fatal autosomal recessive immunodeficiency disease whose rapid and accurate diagnosis is paramount for appropriate treatment. Mutations in STXBP2 gene have been associated with FHL type 5 (FHL-5). Here, we report the first Tibetan Chinese patient diagnosed with FHL-5 caused by a novel compound heterozygous mutation in STXBP2. PATIENT CONCERNS: A 9-year-old girl who presented with recurrent fever, splenomegaly, pancytopenia, hypofibrinogenemia, and conspicuous bone marrow hemophagocytosis was diagnosed with haemophagocytic lymphohistiocytosis (HLH). DIAGNOSIS: FHL mutation analysis of the patient and her parents revealed that she presented compound heterozygosity for STXBP2: a novel missense mutation c.663G > C (p.Glu221Asp) and the known pathogenic splice-site mutation c.1247-1G > C (p.Val417LeufsX126). Bioinformatics analyses predicted that the new mutation was pathogenic and the FHL-5 diagnosis was confirmed. INTERVENTIONS: Upon diagnosis, HLH-2004-directed chemotherapy was instituted, but there was a relapse. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed. OUTCOMES: After transplantation, the patient presented implantation dysfunction, chronic graft-versus-host disease, and 5 episodes of pancreatitis. A follow-up after 5 years revealed that the patient had died of pancreatitis. LESSONS: This finding expands the spectrum of FHL-5-related mutations in Chinese patients and indicates a clear genotype-phenotype correlation of FHL-5 in China.