Vol 13, No 1 (2022)
Review paper
Published online: 2022-05-09

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Hematological manifestations of X-linked lymphoproliferative disease

Natalia Aleksandra Dułak1, Jadwiga Juwa2, Rafał Trzciński1, Alan Majeranowski3, Ninela Irga-Jaworska4
Hematology in Clinical Practice 2022;13(1):1-6.


X-linked lymphoproliferative disease (XLP) is a rare genetic disorder that occurs predominantly in boys. There are two types of the disease, each with different clinical and genetic characteristics. XLP1 is caused by the mutation in the SH2D1A gene and XLP2 is associated with the mutation in XIAP/BIRC gene. Genetic defects lead to the dysfunction of the immune system. Additionally, Epstein-Bárr virus infection plays a major role in the development of the disease. Clinical manifestation varies significantly, even among family members who carry the same mutation. The disease most often manifests with haemophagocytic lymphohistiocytosis, dysgammaglobulinemia, fulminant infectious mononucleosis, splenomegaly, and B-cell lymphomas localized near the ileocecal valve, and colitis. Differential diagnosis should primarily consider more frequent disorders with an impaired immunological response. XLP is a fatal disease, but with the development of new treatment options, patients’ life expectancy has increased significantly. Currently, the only definitive treatment is an early allogeneic hematopoietic stem cell transplantation. The onset of severe symptoms before transplantation largely reduces the patient’s chances of therapeutic success. As a result, it is crucial to make an early diagnosis. New therapies that include enzyme inhibition, gene therapy, and gene editing are very promising. Patients and their families should be provided with genetic counselling and the possibility of preimplantation diagnostics.

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Hematology in Clinical Practice