Clinical and Genetic Spectrum of a Large Cohort of Patients With Leukocyte Adhesion Deficiency Type 1 and 3: A Multicentric Study From India
Authors: Kambli Priyanka Madhav , Bargir Umair Ahmed , Yadav Reetika Malik , Gupta Maya Ravishankar , Dalvi Aparna Dhondi , Hule Gouri , Kelkar Madhura , Sawant-Desai Sneha , Setia Priyanka , Jodhawat Neha , Nambiar Nayana , Dhawale Amruta , Gaikwad Pallavi , Shinde Shweta , Taur Prasad , Gowri Vijaya , Pandrowala Ambreen , Gupta Anju , Joshi Vibhu , Sharma Madhubala , Arora Kanika , Pilania Rakesh Kumar , Chaudhary Himanshi , Agarwal Amita , Katiyar Shobita , Bhattad Sagar , Ramprakash Stalin , CP Raghuram , Jayaram Ananthvikas , Gornale Vinod , Raj Revathi , Uppuluri Ramya , Sivasankaran Meena , Munirathnam Deenadayalan , Lashkari Harsha Prasad , Kalra Manas , Sachdeva Anupam , Sharma Avinash , Balaji Sarath , Govindraj Geeta Madathil , Karande Sunil , Nanavati Ruchi , Manglani Mamta , Subramanyam Girish , Sampagar Abhilasha , CK Indumathi , Gutha Parinitha , Kanakia Swati , Mundada Shiv Prasad , Krishna Vidya , Nampoothiri Sheela , Nemani Sandeep , Rawat Amit , Desai Mukesh , Madkaikar Manisha 
Published: January 2021

Leukocyte adhesion deficiency (LAD) syndrome is a group of inborn errors of immunity characterized by a defect in the cascade of the activation and adhesion leading to the failure of leukocyte to migrate to the site of tissue injury. Three different types of LAD have been described. The most common subtype is LAD type 1 (LAD1) caused due to defects in theITGβ2gene. LAD type 2 (LAD2) is caused by mutations in theSLC35C1gene leading to a generalized loss of expression of fucosylated glycans on the cell surface and LAD type 3 (LAD3) is caused by mutations in theFERMT3gene resulting in platelet function defects along with immunodeficiency. There is a paucity of data available from India on LAD syndromes. The present study is a retrospective analysis of patients with LAD collated from 28 different centers across India. For LAD1, the diagnosis was based on clinical features and flow cytometric expression of CD18 on peripheral blood leukocytes and molecular confirmation by Sanger sequencing. For patients with LAD3 diagnosis was largely based on clinical manifestations and identification of the pathogenic mutation in theFERMT3gene by next-generation Sequencing. Of the total 132 cases diagnosed with LAD, 127 were LAD1 and 5 were LAD3. The majority of our patients (83%) had CD18 expression less than 2% on neutrophils (LAD1°) and presented within the first three months of life with omphalitis, skin and soft tissue infections, delayed umbilical cord detachment, otitis media, and sepsis. The patients with CD18 expression of more than 30% (LAD1+) presented later in life with skin ulcers being the commonest manifestation. Bleeding manifestations were common in patients with LAD3. Persistent neutrophilic leukocytosis was the characteristic finding in all patients. 35 novel mutations were detected in theITGβ2gene, and 4 novel mutations were detected in theFERMT3gene. The study thus presents one of the largest cohorts of patients from India with LAD, focusing on clinical features, immunological characteristics, and molecular spectrum.