Leukocyte Adhesion Deficiency Differential Diagnoses

Updated: Oct 09, 2019
  • Author: Stephen J Nervi, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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DDx

Diagnostic Considerations

These leukocyte adhesion deficiencies (LADs) are unlikely to be confused with hyperimmunoglobulin E syndrome or chronic granulomatous disease because the clinical features of infection resemble those manifested by patients with severe neutropenia despite marked neutrophilia. The neutrophils are mature, showing vacuoles and toxic granulations in the presence of infection, which is easily distinguished from myeloid leukemias.

A defect in a guanosine triphosphate (GTP)-binding protein, Rac2, which is integral to actin-associated neutrophil responses and to the generation of superoxide by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, leads to a clinical syndrome resembling Leukocyte adhesion deficiency with prolonged cord attachment, perirectal cellulitis, and omphalitis associated with marked leukocytosis and poor wound healing. However, integrin expression is intact. The mutation causes dominant-negative inhibition of Rac2-mediated neutrophil functions and low levels of Rac2 protein in the cytosol.

Healthy infants with delayed umbilical cord separation are not uncommon. The absence of leukocytosis distinguishes healthy infants from those with leukocyte adhesion deficiency.