REVUE ALGERIENNE D’ALLERGOLOGIE
Volume 11, Numéro 2, Pages 49-58
2026-07-30

Severe Itgb2-associated Leukocyte Adhesion Deficiency Type 1 In Two Siblings : Early Family-based Diagnosis And Clinical Variability

Authors : Belghazi Meriem . Dehimi Abdelhak . Dridj Nawel . Belaid Brahim . Bioud Belkacem .

Abstract

Introduction: Leukocyte Adhesion Deficiency Type 1 (LAD-I) is a rare autosomal recessive inborn error of immunity caused by pathogenic variants in the ITGB2 gene encoding CD18. Severe forms are associated with impaired leukocyte migration, recurrent infections, persistent neutrophilic leukocytosis, and high mortality in the absence of curative treatment. Case Presentation: We report two siblings from a consanguineous family with severe ITGB2-associated LAD-I. The older sibling was diagnosed at 3 months of age after presenting with a severe necrotic perineal lesion and subsequently developed recurrent gingivostomatitis, bronchiolitis, and osteoarticular involvement. Following identification of the index case, the younger sibling was diagnosed much earlier, at 10 days of life, after developing omphalitis. She later experienced recurrent necrotic perineal lesions and acute gastroenteritis. Both patients exhibited persistent leukocytosis with neutrophilia and markedly reduced CD18 expression (0–2%) on flow cytometry, consistent with severe LAD-I. Whole-exome sequencing identified the same previously reported homozygous pathogenic ITGB2 variant (NM_000211:c.119_128del; p.G40Afs*7) in both siblings. Despite sharing an identical molecular defect and severe immunophenotype, the two children displayed distinct clinical manifestations, illustrating intrafamilial phenotypic variability. Conclusion: This report highlights the importance of family-based screening for early diagnosis of LAD-I and emphasizes that the absence of markedly delayed umbilical cord separation should not exclude the diagnosis. Early immunophenotypic and molecular confirmation remains essential to optimize management and facilitate timely access to curative therapies, including hematopoietic stem cell transplantation (HSCT) and emerging gene therapy approaches.

Keywords

Leukocyte Adhesion Deficiency type 1 LAD-I ; ITGB2 ; CD18 deficiency ; Phenotypic variability