Familial Hemophagocytic Lymphohistiocytosis Syndromes (FHL) are autosomal recessive disorders with heterogeneous genetic origin that occur frequently in the first two years of life. The UNC13D mutation , responsible for %30-40 of all cases , causes FHL Type 3, in which Munc 13-4 protein defect is seen. In FHL Type 3, there is a lack of secretion of cytolytic granules by exocytosis and a significant decrease in NK cell activity.
Here we present clinical and laboratory characteristics ,treatment and outcomes in 3 patients from a single family.
Three children (2year-old-girl, 13mo-old-girl, 3.5 mo-old-boy) of a consanguineous family; were referred to our clinic with fever, paleness and fatigue consecutively. All patients had very light-yellow hair, pale skin, fever and hepatosplenomegaly. Bicytopenia (anemia, thrombocytopenia), hypertriglyceridemia and hyperferritinemia were detected in laboratory and HLH was diagnosed. The first patient died due to heart failure in 9th month of HLH treatment. The second and third patient underwent hematopoietic stem cell transplantation (HSCT) from HLA full matched sibling. Both of them are alive and well at +3 years and at +12 months, respectively. WES analysis revealed a known homozygous mutation in the UNC13D gene in all patients.
FHL is a disease with high relapses and mortality despite immunosuppressive therapy. Early diagnosis by genetic analysis and early HSCT are life-saving in these patients.