OBJECTIVETo introduce the clinical manifestations and laboratory tests of adult onset of primary hemophagocytic syndrome (HPS), and to investigate the essentials of diagnosis and the genotype characteristics in adult onset patient.

METHODSThe definite diagnosis of HPS was made according to HLH-2004. Exons of PRF1, STX11, UNC13D, SH2D1A and RAB27A genes coding region were amplified using polymerase chain reaction.

RESULTSA 48-year-old man was admitted to our hospital because of recurrent fever, pancytopenia and lymph node enlargement. His laboratory test revealed bone marrow hemophagocytosis, elevated ferritin level (2000 µg/L), reduced level of NK cell activity (20.13%) and elevated soluble CD25 level (12277 U/ml). Based on the HLH-2004 diagnostic criteria, the patient was diagnosed as HPS. The patient had viral infection, and no other primary disease was identified that would cause HPS. The patient responded poorly to anti-viral therapy. DNA sequencing was used to confirm that perforin gene mutations might be one of the causes of the patient suffered from primary HPS.

CONCLUSIONSAlthough primary HPS usually affects infants and young children, it also occurred in teens and adults. It is essential to perform genetic screenings to patient whose illnesses recur with unknown causes. In addition, detection of molecular genetic alterations can be used to distinguish primary HPS from acquired HPS.

Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; Male ; Middle Aged ; Perforin ; genetics

Child, Preschool ; Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; therapy ; Male

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by pancytopenia and multiple organ infiltrations of lymphocytes and histiocytes with proliferation and hemohpagocytic activity. HLH is classified as primary (or familial) and secondary. Familial HLH is common in infants and young children, and is related to genetic defects. This article aims to review research advances on PRF1, UNC13D, STX11 and STXBP2, as well as the other 5 genes associated with familial HLH based on molecular genetics, and to summarize diagnosis and treatment methods for this disease.
Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; etiology ; genetics ; therapy ; Molecular Biology

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disease caused by dysregulated immune responses and overwhelming inflammation to infectious or other triggers of the immune system. HLH may be inherited (primary) or may be secondary to any severe infection, malignancy or rheumatologic disease. Clinical progress of HLH is usually rapid and fatal. Early recognition and assessment of potential causes of HLH is critical to improve survival. Urgent treatment is needed for immunosuppression and degradation of the activated antigen. Over the last two decades, research on genetics and pathophysiology of HLH has much improved treatment outcome of the patient. Here, we review recent advances in our understanding of etiology, pathophysiology, diagnosis and treatment of HLH.
Diagnosis ; Genetics ; Humans ; Immune System ; Immunosuppression ; Inflammation ; Lymphohistiocytosis, Hemophagocytic ; Treatment Outcome

Child ; Child, Preschool ; Dexamethasone ; therapeutic use ; Female ; Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; drug therapy ; genetics ; Male ; Prednisolone ; therapeutic use ; Prognosis

DNA Mutational Analysis ; Diagnosis, Differential ; Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; therapy ; Mutation ; genetics ; Perforin ; Pore Forming Cytotoxic Proteins ; genetics ; Qa-SNARE Proteins ; genetics

Central Nervous System Diseases ; etiology ; Child ; Female ; Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic ; complications ; diagnosis ; genetics ; Magnetic Resonance Imaging ; Male ; Mutation ; Perforin ; genetics

OBJECTIVETo analyze mutations in a pedigree of familial hemophagocytic lymphohistiocytosis (FHLH) from Sichuan and provide genetic counseling for the family.

METHODSClinical data of a case with FHLH diagnosed at West China Second Hospital was retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Eight candidate genes for primary HLH were amplified with PCR and analyzed by direct sequencing.

RESULTSThe proband was diagnosed as HLH based on clinical manifestations of recurrent fever for 2 months, hepatosplenomegaly, lymphadenopathy, pancytopenia, hyperferritinemia, and decreased fibrinogen and hemophagocytosis in bone marrow. Genetic testing for primary HLH was carried out considering the relapse of illness after hormone therapy for 8 weeks and the family history. The results of gene sequencing showed that the proband has carried compound heterozygous mutations in PRF1 gene (c.1349C> T in exon 3 and c.445G> A in exon 2). His father has carried a heterozygous mutation (c.445G> A in exon 2) and nonsense mutation (c.900C> T in exon 3), and his mother carried a heterozygous mutation (c.1349C> T in exon 3). Both c.1349C> T and c.445G> A have been previously reported as pathogenic mutations.

CONCLUSIONThe family has been diagnosed as familial HLH type 2 based on clinical and laboratory examinations and molecular genetic testing. Gene sequencing has indicated that is was a recessive type familial HLH.

Base Sequence ; DNA Mutational Analysis ; Exons ; genetics ; Family Health ; Female ; Genes, Recessive ; genetics ; Genetic Predisposition to Disease ; genetics ; Heterozygote ; Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; Male ; Mutation ; Pedigree ; Perforin ; genetics ; Phenotype ; Polymerase Chain Reaction ; Retrospective Studies

Amino Acid Sequence ; Base Sequence ; Child ; Flow Cytometry ; methods ; Genes, X-Linked ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphocytes ; metabolism ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; therapy ; Lymphoproliferative Disorders ; diagnosis ; genetics ; therapy ; Mutation ; Transplantation, Homologous ; X-Linked Inhibitor of Apoptosis Protein ; deficiency ; genetics ; metabolism

No abstract available.
Bone Marrow/metabolism/pathology ; DNA Mutational Analysis ; Gene Rearrangement, T-Lymphocyte ; Humans ; Immunophenotyping ; Infant ; Lymphohistiocytosis, Hemophagocytic/*diagnosis ; Male ; Membrane Proteins/chemistry/genetics ; Polymorphism, Single-Stranded Conformational ; Republic of Korea ; T-Lymphocytes/immunology/*metabolism