Novel STXBP2 Mutation Causing Familial Haemophagocytic Lymphohistiocytosis Type 5 in a Preterm Neonate with Fatal Outcome: A Case Report

Familial Haemophagocytic Lymphohistiocytosis (FHL) is an autosomal recessive disorder characterised by a hyperinflammatory state due to widespread infiltration of organs with macrophages and lymphocytes. Haemophagocytic Lymphohistiocytosis (HLH) presents with fever, hepatosplenomegaly, cytopenia, hyperferritinemia and haemophagocytosis in the reticuloendothelial tissues causing multi organ failure with fatal outcome. HLH is rare in neonates with an incidence of 1 in 50,000 to 1 in 150,000. FHL is diagnosed based on clinical criteria, biochemical abnormalities, and genetic mutation. Mutations involving the gene STXBP2 contributes to around 10% of cases of FHL and there are only a few cases of FHL5 reported from India. A six-week-old neonate presented with sepsis which was unresponsive to antibiotics. Persistent fever, bicytopenia, hepatosplenomegaly and laboratory tests made us suspect HLH, and evaluate further with whole exome sequencing. FHL5 was diagnosed based on the identification of homozygous missense mutation in exon 3 of STXBP2 gene (chr19: 7642803_7642803delA). The baby succumbed to sepsis and multi organ failure. HLH should be considered in the differential diagnosis of any sick infant who presents with prolonged fever, sepsis unresponsive to antibiotics and an unusual clinical course.