Immunodeficiency-73A with defective neutrophil chemotaxis and leukocytosis D81.0

Immunodeficiency-73A with defective neutrophil chemotaxis and leukocytosis (IMD73A) is an immunological disorder characterized by the occurrence of recurrent infections in infancy. Affected infants have periumbilical erythema and later develop skin abscesses and invasive infections.

Very rare, incidence unknown.

Causally, the disease is due to a heterozygous loss-of-function (LOF) mutation in the RAC2 gene (602049) on chromosome 22q13 (Accetta D et al. 2011; Ambruso DR et al. 2000).

Accetta et al (2011) speculated that the mutation results in defective T cell development in the thymus due to defects in migration, adhesion, and proper T cell activation and selection. The heterozygous mutations in the RAC2 gene identified in patients with IMD73A by Ambruso et al. (2000) and Accetta et al. (2011) occurred de novo.

Ambruso et al (2000) reported a male infant from unrelated parents who presented with severe bacterial infections and poor wound healing, suggestive of a neutrophil defect. The infant presented at 5 weeks of age with a perirectal abscess and failure of the umbilical stump to involute. Over the next 4 months, he had recurrent perirectal abscesses, an infected urachal cyst, and nonhealing surgical wounds. Transfusions of neutrophilic granulocytes from healthy blood donors were required for resolution of the abscesses and complete healing of the surgical wounds. The patient had leukocytosis and neutrophilia, normal serum immunoglobulin concentrations, normal complement activity (CH50 and C3), and low-normal numbers of T and B cells for his age. Neutrophil granulocytes showed decreased chemotaxis, F-actin assembly, polarization, impaired PMA- and fMLP-induced azurophil granule secretion and superoxide anion production:expression and upregulation of CD11b was normal. The NADPH oxidase complex functioned normally. Laboratory tests showed leukocytosis, neutrophilia and T-cell lymphopenia. He later presented with fever and periumbilical erythema and a paratracheal abscess positive for Stenotrophamonas and Prevotella species.

Hematopoietic stem cell transplantation can provide a cure.

1. Accetta D et al. (2011) Human phagocyte defect caused by a Rac2 mutation detected by means of neonatal screening for T-cell lymphopenia. (Letter) J Allergy Clin Immun 127: 535-538.
2. Ambruso DR et al (2000) Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc Nat Acad Sci 97: 4654-4659.
3. Lougaris V et al (2020) RAC2 and primary human immune deficiencies. J Leukoc Biol 108: 687-696.
4. Roos D et al. (2021) Hematologically important mutations: the autosomal forms of chronic granulomatous disease (third update). Blood Cells Molec Dis 92: 102596.