X-Linked Lymphoproliferative Syndrome: A Spectrum of Clinical and Immunological Profile and Novel Pathogenic Variants from Chandigarh, India

Author:

Jindal Ankur KumarORCID,Mondal Sanjib,Sil ArchanORCID,Rawat Amit,Chawla Sanchi,Tyagi RahulORCID,Sudhakar Murugan,Banday Aaqib Zaffar,Suri Deepti,Vignesh Pandiarajan,Dhaliwal Manpreet,Sharma Saniya,Rikhi Rashmi,Saka Ruchi,Sharma Rajni,Chatterjee Debajyoti,Sreedharanunni Sreejesh,Uppuluri Ramya,Raj Revathi,Singh Surjit

Abstract

<b><i>Introduction:</i></b> X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. <b><i>Methods:</i></b> We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. <b><i>Results:</i></b> Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of <i>XIAP</i> gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of <i>SH2D1A</i> gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. <b><i>Discussion/Conclusions:</i></b> XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.

Publisher

S. Karger AG

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