X-linked Lymphoproliferative Disease Type 1 Presenting as Lymphoma in a Male Patient With Atypical Common Variable Immunodeficiency Features: A Case of Delayed Diagnosis

TL;DR

A 13-year-old boy with atypical CVID features was later diagnosed with XLP1 after developing lymphoma, highlighting the need for genetic testing in similar cases.

Contribution

This case emphasizes the importance of considering XLP1 in male patients with atypical CVID and early-onset cancer for timely diagnosis.

Findings

XLP1 was diagnosed through whole-exome sequencing despite negative EBV serology.

The patient exhibited atypical CVID features and developed Burkitt lymphoma at age 13.

Early genetic diagnosis can lead to potentially curative treatment for XLP1.

Abstract

X-linked lymphoproliferative disease type 1 (XLP1) is a rare, often fatal primary immunodeficiency (PID) caused by mutations in the SH2D1A gene that result in an uncontrolled immune response to Epstein-Barr virus (EBV) infection. However, a small number of patients do not encounter EBV exposure and exhibit clinical and immunological features similar to those of common variable immunodeficiency (CVID), leading to delayed diagnosis. Herein, we report the case of a 13-year-old boy diagnosed at eight years of age with CVID after he experienced recurrent pneumonias, hypogammaglobulinemia, and chronic bronchiectasis. He was given monthly intravenous immunoglobulin (IVIG) for five years. At 13 years of age, he presented with abdominal pain, and imaging studies demonstrated a bulky retroperitoneal mass, which was confirmed by biopsy to be Burkitt lymphoma. Immunophenotyping revealed low CD4⁺ T cells and B cells, as well as an inverted CD4⁺ to CD8⁺ T-lymphocyte ratio (CD4⁺/CD8⁺). A diagnosis of XLP1 was established through whole-exome sequencing, in the presence of negative EBV serology, which revealed a hemizygous pathogenic variant of SH2D1A. He was managed with chemotherapy and evaluated for hematopoietic stem cell transplant. This case highlights the significance of including monogenic immunodeficiencies in the differential diagnosis of male patients with atypical CVID phenotypes and early-onset cancer. Presymptomatic genetic diagnosis can enable early and potentially curative diagnosis and treatment.

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