Leucocyte adhesion deficiency-A multicentre national experience.

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• Leukocyte adhesion deficiency (LAD) encompasses three rare, inherited autosomal recessive immunodeficiency subtypes.
• Patients often present with severe infections, high white blood cell counts, and delayed umbilical cord detachment.

Purpose of the Study:

• To characterize the phenotypic, genotypic, and biochemical profiles of LAD-I, LAD-II, and LAD-III subtypes.
• To identify novel mutations and assess treatment outcomes, including hematopoietic stem cell transplantation (HSCT).

Main Methods:

• Analysis of 29 patients diagnosed with LAD subtypes in Israeli and Palestinian medical centers.
• Phenotypic, genotypic, and biochemical assessments including CD18, CD11a, and SLeX expression, H antigen status, and platelet function tests.
• Genetic sequencing to identify mutations in ITGB2 and FERMT3 genes.

Main Results:

• LAD-I showed variable CD18 and negligible CD11a expression. LAD-II presented with distinct facial features, malformations, and Bombay blood group (hh). LAD-III involved inactive β2 integrins, bleeding disorders, and thrombocytopenia.
• Two novel mutations were identified: c.1099delG in ITGB2 (LAD-I) and c.1069C>T in FERMT3 (LAD-III).
• HSCT was successful in eight LAD-I and LAD-III patients. Cumulative survival rates were 75% (LAD-I), 50% (LAD-II), and 40% (LAD-III) with median follow-up periods ranging from 3.25 to 6 years.

Conclusions:

• Comprehensive characterization of LAD subtypes aids in diagnosis and management.
• Genetic analysis and specific biomarker assessment are crucial for differentiating LAD subtypes.
• Prenatal diagnosis is recommended for families with a history of LAD syndromes.