Clinical characteristics of male patients with childhood-onset neutropenia
| . | Age of onset/ current . | TLR8 variant (frequency in blood if mosaic) . | Presenting symptoms . | Cytopenias . | Other major features . | Bone marrow . | Current status . |
|---|---|---|---|---|---|---|---|
| P1 | 15 y | p.P432L (14%) | Infection: Clostridium septicum bacteremia | Neutrophils, RBCs, platelets, B cells | HSM, liver with hemophagocytosis, low IgG | Well organized lymphoid aggregates, normocellular, T-cell clonality (Vg10 Jg1/2, 66%) | Stable on G-CSF and corticosteroids |
| 18 y | |||||||
| P2 | 1 yDec 4 y | p.P432L (18%) | Infection: Pneumonia and otitis media | Neutrophils, RBCs | HSM, low IgG | Agranulocytosis, normal myeloblasts, normocellular | Died following MMURD (9/10) × 2 |
| P3 | 7 y | p.F494L (8%) | Infection: lymphadenitis | Neutrophils, platelets | HSM, low IgG | Hypocellular with myeloid hypoplasia, lymphohistocytic aggregates, expanded TCRγ/δ T-cell population | Stable on G-CSF |
| 19 y | |||||||
| P4 | 16 y27 y | p.P432L (26%) | Infection: Nocardia | Neutrophils, RBCs, Platelets, B cells | HSM, low IgG | Agranulocytosis, oligoclonal CD8+ population (Vb1 CD8+) | Alive >3 y following haplo-identical HCT |
| P5 | 5 y20 y | p.P432L (17%) | ITP (age 5 y) infections (age 16 y) | Neutrophils, platelets | Splenomegaly, lymphadenopathy, recurrent GI inflammation/infection, type I DM | Hypocellular with myeloid hypoplasia, T-cell predominant lymphohistiocytic aggregates | Alive 100 d post MRD HST |
| P6 | 9 moDec 8 y | p.G527D (germline) | Infection: otitis media, fungal infections | Neutrophils, RBCs, platelets | HSM, lymphadenopathy, low IgG | Hypocellular with myeloid hypoplasia and fibrosis | Died due to infection |
| . | Age of onset/ current . | TLR8 variant (frequency in blood if mosaic) . | Presenting symptoms . | Cytopenias . | Other major features . | Bone marrow . | Current status . |
|---|---|---|---|---|---|---|---|
| P1 | 15 y | p.P432L (14%) | Infection: Clostridium septicum bacteremia | Neutrophils, RBCs, platelets, B cells | HSM, liver with hemophagocytosis, low IgG | Well organized lymphoid aggregates, normocellular, T-cell clonality (Vg10 Jg1/2, 66%) | Stable on G-CSF and corticosteroids |
| 18 y | |||||||
| P2 | 1 yDec 4 y | p.P432L (18%) | Infection: Pneumonia and otitis media | Neutrophils, RBCs | HSM, low IgG | Agranulocytosis, normal myeloblasts, normocellular | Died following MMURD (9/10) × 2 |
| P3 | 7 y | p.F494L (8%) | Infection: lymphadenitis | Neutrophils, platelets | HSM, low IgG | Hypocellular with myeloid hypoplasia, lymphohistocytic aggregates, expanded TCRγ/δ T-cell population | Stable on G-CSF |
| 19 y | |||||||
| P4 | 16 y27 y | p.P432L (26%) | Infection: Nocardia | Neutrophils, RBCs, Platelets, B cells | HSM, low IgG | Agranulocytosis, oligoclonal CD8+ population (Vb1 CD8+) | Alive >3 y following haplo-identical HCT |
| P5 | 5 y20 y | p.P432L (17%) | ITP (age 5 y) infections (age 16 y) | Neutrophils, platelets | Splenomegaly, lymphadenopathy, recurrent GI inflammation/infection, type I DM | Hypocellular with myeloid hypoplasia, T-cell predominant lymphohistiocytic aggregates | Alive 100 d post MRD HST |
| P6 | 9 moDec 8 y | p.G527D (germline) | Infection: otitis media, fungal infections | Neutrophils, RBCs, platelets | HSM, lymphadenopathy, low IgG | Hypocellular with myeloid hypoplasia and fibrosis | Died due to infection |
Dec, deceased; DM, diabetes mellitus; GI, gastrointestinal; HCT, hematopoietic cell transplantation; HSM, hepatosplenomegaly; ITP, idiopathic thrombocytopenia; MMURD, mismatched unrelated donor; MRD, matched related donor; RBC, red blood cell.