Rationale: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessively inherited disease and can be divided into five types. The mortality of untreated patients is up to 95% and it can be healed only after immunochemotherapy for disease control and hematopoietic stem cell transplantation. Clinical data of a girl with late-onset and recurrent hemophagocytic lymphohistiocytosis (HLH) was retrospectively analyzed to determine the etiology and potential pathogenic gene.
Patient concerns and clinical findings: The proband was a female child patient from a consanguineous marriage family who was 11 years old, and clinically manifested delayed (onset at the age of 4 years and 6 months) and recrudescent HLH. Both of her elder brothers died at the ages of 4 and 5 years, respectively. The patient had a degranulation function defect of CD107a in natural killer (NK) cells, and the degranulation function of cytotoxic T lymphocytes (CTL) obviously declined (ΔMFI: 1.4%, normal ≧2.8%); the degranulation function of NK cells and CTL of her father was also obviously reduced. To identify possible underlying genetic causes, gene mutation analysis was undertaken. A novel homozygous nonsense mutation in STX11 (c.49C>T, p.Q17X) was documented, arising from both her parents.
Diagnosis: According to the clinical manifestations and detection results of STX11, the diagnosis of FHL-type 4 was confirmed and her parents were heterozygotic carriers.
Interventions and outcomes: Good responses to HLH-2004 chemotherapy had been achieved for each onset, and the maximum remission duration (without taking any drug) was 23 months. The patient has been alive for 82 months since the onset, and has stopped taking dexamethasone and etoposide, but is still on oral cyclosporine to maintain the treatment. She has performed HLA matching and now is actively looking for a donor to prepare hematopoietic stem cell transplantation.
Conclusions: Relevant gene detections should be implemented at the earliest for young patients from consanguineous marriages and with a family history of HLH so as to provide a basis for etiological diagnosis and radical treatment by hematopoietic stem cell transplantation and provide accurate genetic counseling for family members.