Rare and Heterogeneous manifestations of Leucocyte adhesion deficiency type 1: Report of two cases with diagnostic dilemmas and Novel ITGB mutation.

Abstract

Abstract Background: Primary immunodeficiency disorders (PID) are rare disorders with heterogeneous manifestations, overlapping with other diseases such as autoimmunity, malignancy, and infections. This makes the diagnosis very challenging and delays management. Leucocyte adhesion defects (LAD) are a group of PIDs in which patients lack adhesion molecules on leukocytes needed for their emigration through blood vessels to the site of infection. Patients with LAD can present with diverse clinical features including severe and life-threatening infections, early in life, and the absence of pus formation around infection or inflammation. There is often delayed umbilical cord separation, omphalitis, late wound healing, and a high white blood cell count. If not recognized and managed early, can lead to life-threatening complications and death.Case Presentation:LAD 1 is characterized by a mutation in integrin subunit beta 2 (ITGB2). We report two cases of LAD1 with unusual presentations (post-circumcision excessive bleeding and granulomatous inflammation of the right eye) which were confirmed by flowcytometric analysis and genetic testing. In one case we found a novel ITGB2 mutation (c.994‒1G>C; splice site variant).Conclusions:These cases highlight the importance of a multidisciplinary approach to recognizing clues in patients with uncommon manifestations of a rare disease. This led to the proper diagnostic workup of primary immunodeficiency disorder leading to a better understanding of the disease, appropriate patient counseling, and being better equipped to deal with complications.