Abstract
Summary
Genetic neutropenia comprises heterogeneous phenotypes with variable patterns and severity of infectious complications. However, comparative real‐world data on subtype‐specific infectious complications remain limited. We analysed patients with genetic neutropenia enrolled in the Canadian Inherited Marrow Failure Registry between 2001 and 2025. Patients were classified into severe congenital neutropenia (SCN), cyclic neutropenia, syndromic neutropenia or suspected genetic neutropenia (SGN). Infectious complications were classified by type and severity. Eighty‐nine patients were included, including SCN (
n
= 27), cyclic neutropenia (
n
= 13), syndromic neutropenia (
n
= 25) and SGN (
n
= 24).
Elastase, neutrophil expressed (ELANE)
variants were most common (
n
= 30) and predominated in SCN and cyclic neutropenia, whereas syndromic neutropenia included
tafazzin (TAZ), solute carrier family 37 member 4 (SLC37A4), vacuolar protein sorting 13 homolog B (VPS13B), C‐X‐C motif chemokine receptor 4 (CXCR4), glucose‐6‐phosphatase catalytic subunit 3 (G6PC3), signal recognition particle 54 (SRP54)
and
HCLS1 associated protein X‐1 (HAX1)
variants. Overall, 68 patients (76.4%) experienced ≥1 infectious complication and 45 (50.6%) developed severe infections. Febrile neutropenia occurred more frequently in SCN (59.3%) than in other subtypes (
p
= 0.005), while skin and soft tissue infections were more common in syndromic neutropenia (56.0%) and SCN (44.4%) (
p
= 0.038). Granulocyte colony‐stimulating factor was administered in 60 patients, with an overall response rate of 90.0%. Ten patients underwent haematopoietic stem cell transplantation. Infection patterns differed across genetic neutropenia subtypes, supporting subtype‐informed surveillance and management.