A newborn boy has delayed separation of the umbilical cord, recurrent necrotic skin infections without pus formation, and a total leukocyte count of 42,000 per microlitre with marked neutrophilia. Flow cytometry shows absence of CD18 expression. What is the underlying defect?

• A Defective phagolysosome fusion due to a lysosomal trafficking regulator mutation
• B Defective chemoattractant receptor signalling through formyl peptide receptors
• C Failure of NADPH oxidase assembly in the phagosome membrane
• D Absence of beta-2 integrins required for firm adhesion of neutrophils to endothelium ✓

Explanation

Leukocyte adhesion deficiency type I results from mutations in the ITGB2 gene encoding CD18, the beta chain shared by LFA-1, Mac-1 and p150,95 integrins. Without these integrins, neutrophils roll along endothelium but cannot achieve firm adhesion or transmigration, producing neutrophilia, absent pus and delayed cord separation. NADPH oxidase failure defines chronic granulomatous disease, and defective lysosomal trafficking defines Chediak-Higashi syndrome.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.