Summary of patient data
| . | Patient 1 . | Patient 2* . | Patient 3 . | Patient 4 . | Patient 5† . | Patient 6 . | Patient 7 . | Patient 8* . | Patient 9 . | Patient 10† . |
|---|---|---|---|---|---|---|---|---|---|---|
| BIRC4 mutation | Deletion Exon 6 | Deletion Exons 1–5 | 1445C>G (P482R) | 1481T>A (I494N) | 563G>A (G188E) | 868–869insT (Y290fsX294) | 997C>T (Q333X) | Deletion Exons 1–5 | 310C>T (Q104X) | 563G>A (G188E) |
| XIAP expression‡ | Truncated, decreased | Not detectable | Decreased | Not tested | Decreased | Not detectable | Not detectable | Not detectable | Not detectable | Decreased |
| Age at initial HLH presentation | Infancy | Infancy | Infancy | Infancy | Infancy | 4 years | 6 years | 7 years | 8 years | Asymptomatic |
| Recurrent HLH | + | + | NA, prompt HCT | NA, prompt HCT | NA, prompt HCT | + | + | Recurrent cytopenias, prolonged viral illnesses | Recurrent fevers, prolonged viral illnesses | −¶ |
| Fever | + | + | + | + | + | + | + | + | + | − |
| Splenomegaly | + | + | + | + | + | + | + | + | + | − |
| Hepatitis | + | + | + | + | + | + | + | Unknown | + | − |
| Bicytopenia | + | + | + | + | + | + | + | + | + | − |
| Hypertriglyceridemia | + | + | + | + | + | + | Unknown | Unknown | + | − |
| Hypofibrinogenemia | + | + | + | + | + | + | Unknown | Unknown | + | − |
| Hemophagocytosis | − | + | + | + | + | − | − | Unknown | − | − |
| Hyperferritinemia | + | + | + | + | + | + | Unknown | Unknown | + | − |
| Elevated soluble IL2R | + | + | + | + | + | + | Unknown | Unknown | + | − |
| CNS symptoms | − | − | + (seizure) | − | − | − | − | − | − | − |
| Pathologic CSF | + | − | + | − | − | NT | NT | NT | − | − |
| EBV-associated HLH | − | − | − | − | − | + | − | + | + | − |
| CMV-associated HLH | − | + | − | − | − | + | − | − | − | − |
| Hypogammaglobulinemia | +§ | −§ | −§ | −§ | NT | − | − | − | + | − |
| Treatment | Liver transplantation; tacrolimus prednisone | Prednisone; cyclosporine | HLH 2004, including IT treatment | HLH 2004 alemtuzumab | HLH 2004 etanercept | Supportive care | Supportive care | Supportive care | Dexamethasone; rituximab | − |
| Allogeneic HCT | + | + | + | + | + | − | − | − | + | + |
| Current age | 12 y | 4 y | Deceased | 3 y | Deceased | 24 y | 16 y | 28 y | Deceased | 4 y |
| Family history | Yes | Yes | No | No | (No)‖ | No | No | Yes | Yes | Yes |
| . | Patient 1 . | Patient 2* . | Patient 3 . | Patient 4 . | Patient 5† . | Patient 6 . | Patient 7 . | Patient 8* . | Patient 9 . | Patient 10† . |
|---|---|---|---|---|---|---|---|---|---|---|
| BIRC4 mutation | Deletion Exon 6 | Deletion Exons 1–5 | 1445C>G (P482R) | 1481T>A (I494N) | 563G>A (G188E) | 868–869insT (Y290fsX294) | 997C>T (Q333X) | Deletion Exons 1–5 | 310C>T (Q104X) | 563G>A (G188E) |
| XIAP expression‡ | Truncated, decreased | Not detectable | Decreased | Not tested | Decreased | Not detectable | Not detectable | Not detectable | Not detectable | Decreased |
| Age at initial HLH presentation | Infancy | Infancy | Infancy | Infancy | Infancy | 4 years | 6 years | 7 years | 8 years | Asymptomatic |
| Recurrent HLH | + | + | NA, prompt HCT | NA, prompt HCT | NA, prompt HCT | + | + | Recurrent cytopenias, prolonged viral illnesses | Recurrent fevers, prolonged viral illnesses | −¶ |
| Fever | + | + | + | + | + | + | + | + | + | − |
| Splenomegaly | + | + | + | + | + | + | + | + | + | − |
| Hepatitis | + | + | + | + | + | + | + | Unknown | + | − |
| Bicytopenia | + | + | + | + | + | + | + | + | + | − |
| Hypertriglyceridemia | + | + | + | + | + | + | Unknown | Unknown | + | − |
| Hypofibrinogenemia | + | + | + | + | + | + | Unknown | Unknown | + | − |
| Hemophagocytosis | − | + | + | + | + | − | − | Unknown | − | − |
| Hyperferritinemia | + | + | + | + | + | + | Unknown | Unknown | + | − |
| Elevated soluble IL2R | + | + | + | + | + | + | Unknown | Unknown | + | − |
| CNS symptoms | − | − | + (seizure) | − | − | − | − | − | − | − |
| Pathologic CSF | + | − | + | − | − | NT | NT | NT | − | − |
| EBV-associated HLH | − | − | − | − | − | + | − | + | + | − |
| CMV-associated HLH | − | + | − | − | − | + | − | − | − | − |
| Hypogammaglobulinemia | +§ | −§ | −§ | −§ | NT | − | − | − | + | − |
| Treatment | Liver transplantation; tacrolimus prednisone | Prednisone; cyclosporine | HLH 2004, including IT treatment | HLH 2004 alemtuzumab | HLH 2004 etanercept | Supportive care | Supportive care | Supportive care | Dexamethasone; rituximab | − |
| Allogeneic HCT | + | + | + | + | + | − | − | − | + | + |
| Current age | 12 y | 4 y | Deceased | 3 y | Deceased | 24 y | 16 y | 28 y | Deceased | 4 y |
| Family history | Yes | Yes | No | No | (No)‖ | No | No | Yes | Yes | Yes |
HCT indicates hematopoietic cell transplantation;CNS, central nervous system; EBV, Epstein-Barr virus; CMV, cytomegalo virus; NA, not applicable; and NT, not tested.
Patients 2 and 8 are maternally related.
Patients 5 and 10 are maternally related.
As determined by Western blotting and/or intracellular flow cytometry.
Tested while on immunosuppressive therapy.
Maternally related to patient 10 who was asymptomatic at the time of diagnosis.
Patient was diagnosed and treated with allogeneic HCT before being symptomatic.