Severe congenital neutropenia with mastoidectomy: A case report of HAX1

Introduction

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency syndrome that is characterized by persistent severe neutropenia and increased susceptibility to bacterial and fungal infections in early infancy (Boztug K et al., Curr Opin Immunol 2009; 21(5): 472–480).

Rolf Kostmann has first identified the disease in Swedish patients in 1956 with the name of infantile genetic agranulocytosis (Kostmann R et al., Acta Paediatr Suppl 1956; 45(Suppl 105): 1–78). Multiple genetic defects have been reported in different forms of SCN such as neutrophil elastase (ELANE) gene, HCLS-associated protein X-1 (HAX1), glucose 6 phosphatase catalytic subunit 3 (G6PC3), growth factor independent-1 (GFI1) (Boztug K et al., Curr Opin Immunol 2009; 21(5): 472–480). Autosomal recessive mutations in HAX1 were described in 2007 as the genetic defect in the Kostmann patients (Klein C et al., Nat Genet 2007; 39: 86–92). A maturation arrest characterizes it at the stage of promyelocytes/myelocytes in bone marrow. Peripheral blood absolute neutrophil counts (ANC) are below 0.5×10⁹/L. Life-threatening systemic bacterial infections (e. g., pneumonitis and abscesses) from early infancy always accompany. Oral ulcerations, gingivitis and stomatitis are also present in patients by two years of age. Blood monocytes and eosinophil counts and the level of serum immunoglobulins are usually elevated, whereas anti-neutrophil-specific antibodies are absent. Granulocyte colony-stimulating factor (G-CSF) is the first-line treatment for Kostmann disease (Welte K et al., Hematol Oncol Clin North Am 2009; 23(2): 307–320). Further, patients with SCN, including Kostmann disease, are at increased risk for developing myelodysplastic syndrome/ acute myeloid leukemia. Hematopoietic stem cell transplantation remains the only currently available treatment for refractory cases to G-CSF and patients who have transformed into myelodysplastic syndrome/ leukemia (Zeidler C et al., Br J Haematol 2009; 144(4): 459–467).

We report here the case of a child with chronic mastoiditis who was diagnosed late with Kostmann disease. He was treated successfully by G-CSF, antibiotics, and surgically.

Publication History

Article published online:
08 June 2021