An atypical adolescent case of leukocyte adhesion deficiency I caused by a novel <i>ITGB2</i> splicing variant with successful immune reconstitution following hematopoietic stem cell transplantation

Leukocyte adhesion deficiency I (LAD-I) is an autosomal recessive immunodeficiency caused by mutations in the ITGB2 gene, characterized by recurrent severe infections, impaired pus formation, and delayed wound healing. In this study, we describe a late-onset presentation of LAD-I in a 22-year-old male who initially exhibited marked leukocytosis and neonatal omphalitis, followed by recurrent upper respiratory tract infections from 9 months of age. At age 13, the patient developed abdominal and left iliac fossa abscesses, which progressed to a vesicocutaneous fistula after a prolonged febrile episode. Extended catheterization and antibiotic treatment led to the formation of characteristic tin foil-like scarring. Recurrent purulent skin and soft tissue infections led to widespread scarring and pigmentary changes. Next-generation sequencing (NGS) identified a novel homozygous splice-site mutation in ITGB2 (NM_000211.5, c.1225-1G > A, IVS10-1G > A). In silico analysis predicted disruption of the acceptor site, while a minigene assay demonstrated two aberrant splicing events, namely a 12-bp deletion and complete skipping of exon 11 (188 bp). Flow cytometry analysis at age 13 showed CD18 expression reduced to less than 1% across granulocytes, monocytes, and lymphocytes, with concomitant decreases in β2-integrin α subunits (CD11a, CD11b, and CD11c). At 15 years of age, the patient underwent hematopoietic stem cell transplantation (HSCT) from a fully HLA-matched (10/10) heterozygous sister donor following a modified myeloablative conditioning regimen. Although initial chimerism fluctuated, full donor chimerism was ultimately achieved, restoring CD18 expression and normalizing ɑ-integrin levels. This study highlights the therapeutic efficacy of HSCT in correcting the molecular defects associated with LAD-I.