Leukocyte Adhesion Deficiency-I: Clinical and Molecular Characterization in an Indian Population

To describe clinical and flow cytometric immunophenotyping details of 26 patients of Leukocyte adhesion deficiency-I (LAD-I) along with molecular characterization of 7 patients.

Diagnosis of LAD-I was suspected on the basis of clinical features, white blood cell count and absolute neutrophil counts and flow cytometric assessment of expression of CD18 and CD11(a, b, c) on leukocytes. Mutation analysis was performed using DNA PCR and conformation sensitive gel electrophoresis (CSGE) technique followed by sequencing.

All the patients were symptomatic by the age of 6 mo, with history of recurrent bacterial infections involving skin, mucosa or umbilical cord (omphalitis) being the most frequent presenting symptoms. White blood cells (WBC) and absolute neutrophil counts (ANC) were markedly elevated, without any specific morphological findings. On flow cytometry, CD11a and CD11c showed moderate correlation with CD18 expression. Mutation analysis was performed in 7 patients and six different mutations (4 missense, 2 nonsense and 1 splice site) were identified, all of which were homozygous in nature.

A presentation of repeated bacterial infections during infancy, especially omphalitis, with markedly elevated absolute neutrophil counts should trigger investigations for LAD-I including flow cytometric analysis of CD11/CD18 expression.