What Is X-linked Lymphoproliferative Syndrome?
The X-linked lymphoproliferative syndrome is a rare inherited immunodeficiency disorder affecting the immune system and the blood-forming cells. The X-linked lymphoproliferative syndrome is mainly of two types - genetically inherited, also called XPL1, and lymphoproliferative disease, also called XPL2. Individuals affected with X-linked lymphoproliferative syndrome can not regulate the immune system to fight against infections and diseases; generally, it is most likely to be associated with exposure to Epstein Barr Virus (EBV), which can cause some life-threatening conditions involving infectious mononucleosis, fulminant hepatitis, hypogammaglobulinemia which refers to the abnormal ranges of antibodies and body secretions.
What Are the Causes of X-Linked Lymphoproliferative Syndrome?
The X-linked lymphoproliferative syndrome is a rare disorder caused by the inheritance of the mutation of genes. It has a chromosomal-linked recessive pattern. Chromosomes are the carriers of the genetic material or information present in the nucleus of the cell; generally, a body has 46 chromosomes X and Y, which are paired with each other from 1 to 22, then they have sex chromosomes. In males, there is one X and one Y sex chromosome; in females, all the pairs have X sex chromosomes. The disorders can be inherited by either parent or by a single parent. X-linked disorders are referred to as defective genes present on the X chromosome; as females have two x chromosomes, one of the chromosomes will be inactive or turned off, which means the defective gene will be present on the other X chromosome.
So, the chances of getting affected by the disease are less, though females can be the carriers of the disease without showing any signs and symptoms throughout their lifetime. In contrast, in males, the chances of getting the disease are higher than in females because they have one X chromosome with the defective gene present, which will cause the disease.
The gene responsible for causing X-linked lymphoproliferative syndrome is named SH2D1A. In the studies, it is observed that the defective gene SH2D1A has a protein SAP, which manages another protein called – SLAM (signaling lymphocytic activation molecule), which regulates T-cells and B-cells. The defect in the gene SH2D1A will affect the controlling function of SLAM and cause immunodeficiency.
What Are the Signs and Symptoms of X-Linked Lymphoproliferative Syndrome?
The X-linked lymphoproliferative syndrome is a chromosomal-linked recessive inherited disorder generally associated with Epstein Barr virus, which does not lead to long-lasting side effects, usually asymptomatic but can cause other systemic conditions like infectious mononucleosis, fulminant hepatitis, hypogammaglobulinemia, T-cell involving malignancies, and other abnormal conditions. Individuals with X-linked lymphoproliferative syndrome tend to develop infectious mononucleosis causing high-grade fever, sore throat (pharyngitis), enlarged lymph nodes, splenomegaly (enlarged spleen), hepatomegaly (enlarged liver), paleness over the skin, jaundice. In some cases of infectious mononucleosis, it can lead to life-threatening conditions by excessive proliferation of white blood cells, bone marrow failure, aplastic anemia, and thrombocytopenia.
The syndrome also affects the body's immune system, causing antigen-antibody reactions leading to decreased levels of antibodies or immunoglobulin and other body secretions, also called acquired hypogammaglobulinemia. Due to the low levels of antibodies, the patient becomes more susceptible to other recurrent infections.
The X-linked lymphoproliferative syndrome leads to the development of certain malignancies or lymphomas involving B-cells. For example, Burkitt's lymphoma is associated with abdominal swelling or distention, dysfunctions in the absorption process of the gastrointestinal tract, vomiting, diarrhea, weakness, fatigue, and weight loss. Hemophagocytic lymphohistiocytosis is caused by the abnormal proliferation of T-cells and B-cells, which are also associated with X-linked lymphoproliferative syndrome.
What Are the Other Names for X-Linked Lymphoproliferative Syndrome?
The X-linked lymphoproliferative syndrome is also known as
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Duncan’s Disease.
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Epstein Barr Virus Susceptibility.
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Epstein Barr Virus-Induced lymphoproliferative disease in males.
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Immunodeficiency-5 (IMD5).
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Purtilo Syndrome.
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X-linked progressive combined variable immunodeficiency.
What Are the X-Linked Lymphoproliferative Syndrome-Related Disorders?
The X-linked lymphoproliferative syndrome is characterized by immunodeficiency disorder, which affects the body's immune system and blood-forming cells.
The related disorders are:
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Hemophagocytic Lymphohistiocytosis - Severe immune system disorder causing an overactive immune response.
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Epstein Barr Virus: A common virus linked to infectious mononucleosis and other illnesses.
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Hypogammaglobulinemia: Low levels of immunoglobulins, leading to weakened immune function.
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Gastrointestinal Tract Dysfunction: Impaired digestive and absorptive functions within the gastrointestinal system.
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Burkitt's Lymphoma: Aggressive form of non-Hodgkin lymphoma associated with Epstein Barr Virus.
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Infectious Mononucleosis: Viral illness causing fatigue, sore throat, and swollen lymph nodes, often caused by Epstein Barr Virus.
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T-cells and B-cells are related to lymphomas.
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Liver diseases.
What Are the Investigations for the Diagnosis of X-Linked Lymphoproliferative Syndrome?
The X-linked lymphoproliferative syndrome can be diagnosed by the following investigations -
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The X-linked lymphoproliferative syndrome is an inherited disease caused by gene mutation, so recording a patient's personal and family history is very important.
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A physical examination is done to understand the signs and symptoms of the patient. The physical examination involves inspections, palpitations, acculturation, and evaluations.
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Genetic testing is done to determine the gene involved and the cause of the disorder.
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Complete Blood Count - It is a blood test that is performed to determine the count of blood cells, like red blood cells, white blood cells, and platelets.
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Antigen-antibodies Testing - It is advised to perform this test to check the level of antibodies in the blood.
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Ultrasound Sonography - An ultrasound test is advised to check internal organs like the liver and spleen.
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MRI (Magnetic Resonance Imaging) - It is an imaging test done to determine the extent of the disorders and organs involved.
What Are the Treatment Modalities of X-Linked Lymphoproliferative Syndrome?
The X-linked lymphoproliferative syndrome is a treatable condition if it is diagnosed early.
The following are the treatment modalities for X-linked lymphoproliferative syndrome:
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Infusion of Immunoglobulins - In this condition, the level of antibodies or immunoglobulins gets lower, so the patient's body cannot fight against the infections. Therefore, immunoglobulins are infused intravenously into the patient.
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Antibiotic Therapy - It is indicated to give antibiotic treatment to the patient to fight against other infections.
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Genetic Counseling - X-linked lymphoproliferative syndrome is a genetic disorder; therefore, giving a counseling session to the patient and their family members is important.
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The X-linked lymphoproliferative syndrome can lead to associated lymphomas that need radiation or chemotherapy to recover.
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Symptomatic and supportive treatment is also required.
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The administration of steroids is indicated in immunodeficient disorders.
Conclusion
The X-linked lymphoproliferative syndrome is an extremely rare disorder affecting the body's immune system and exclusively affects males more than females. It is mostly associated with the Epstein-Barr virus and its complications which can lead to life-threatening conditions. A team of specialist doctors is required to treat the disease, including immunologists, hematologists, oncologists, and physicians.
