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X-Linked Lymphoproliferative Disorder

X Linked Lymphoproliferative Syndrome


Presentation

  • Herein we present the clinical and pathologic findings for the first known case of X-linked lymphoproliferative disorder with visual symptoms at initial presentation.[ncbi.nlm.nih.gov]
  • Survivors may go on to develop an acquired hypogammaglobulinaema, red cell aplasia, aplastic anaemia or lymphomatoid granulomatosis. [ 2, 3 ] Presentation Patients present in childhood (mean age 3-5 years) with signs of EBV infection: Respiratory : pharyngitis[patient.info]
  • Rarely, severe anemia, thrombocytopenia, and inflammation of the blood vessels may also present in those patients. Onset of symptoms ranges from six months to 10 years of age.[cags.org.ae]
  • When alterations in the SH2D1A gene are present, usually less SAP protein is produced. Occasionally, an abnormal protein is produced, but it is unable to function properly.[chop.edu]
Cervical Lymphadenopathy
  • He developed progressive cervical lymphadenopathy and cerebellar dysfunction.[ajnr.org]
Generalized Lymphadenopathy
  • Bahrain Al-Mukharraq (1997) described a 49-month-old Bahraini boy who presented at the age of six months with history of upper respiratory tract infection, pallor, generalized lymphadenopathy, hepatosplenomegaly, and delayed milestones.[cags.org.ae]
Infectious Mononucleosis
  • mononucleosis–IM, severe hypogammaglobulinemia–ergo susceptibility to various infections, B-cell lymphomas Clinical Onset between 6 months and 10 yrs of age; half of Pts have IM characterized by fever, pharyngitis, lymphadenopathy, splenomegaly, hepatomegaly[medical-dictionary.thefreedictionary.com]
  • This X-linked immunodeficiency becomes evident when the patients are infected with Epstein Barr virus (EBV) and develop a fulminant form of infectious mononucleosis leading to a lymphoproliferative syndrome that is often fatal (X-linked lymphoproliferative[pesquisa.bvsalud.org]
  • Over 70% of patients die by the age of 10 due to fatal infectious mononucleosis. Malignant lymphoma was associated in 30% of XLP cases, however, a literature search revealed no reports involving primary lesions of the nasal sinus.[jstage.jst.go.jp]
  • mononucleosis HLH — hemophagocytic lymphohistiocytosis NKT — natural killer T lymphocytes XLP — X-linked lymphoproliferative disorder Copyright 2012 by the America Academy of Pediatrics View Full Text Log in using your username and password Log in through[pediatrics.aappublications.org]
High Fever
  • FIM/HLH may be related to the following signs and symptoms: High fever Enlarged spleen Low levels of blood cells, including white blood cells (immune cells), red blood cells (cells that carry oxygen to body tissues), and platelets (cells that help the[stjude.org]
  • For children with a functioning immune system, a typical response to Epstein-Barr virus can include: Swollen lymph nodes (glands in the neck, under the arm, or in the groin) Sore throat High fever Lack of energy, tiredness Enlargement of the liver and[chop.edu]
  • fever • Lack of energy, tiredness • Enlargement of the liver and/or spleen • Muscle aches and pains Since the immune system of individuals with Epstein-Barr virus (EBV) does not function properly in response to the virus, potentially severe complications[checkorphan.org]
Night Sweats
  • People with the condition should watch closely for general signs or symptoms of lymphoma, including the following: One or more firm or enlarged lymph nodes (glands) Feeling tired Fever Weight loss Night sweats Trouble breathing If any of these signs or[stjude.org]
  • Instead, boys and men with XLP1 should be seen on a regular basis by their physicians and remain aware of the signs and symptoms of lymphoma, such as development of one or more firm and/or enlarged lymph nodes, fatigue, fever, weight loss, night sweats[chop.edu]
  • sweats and shortness of breath.[checkorphan.org]
  • In July 2001, the patient presented with malaise, weight loss, night sweats, and fever.[ajnr.org]
Cotton Wool Spots
  • When a young patient presents with cotton wool spots, a thorough workup must be done, and immunologic disorders should be considered in the differential diagnosis.[ncbi.nlm.nih.gov]
Denial
  • If your application is denied, you are entitled to an appeals process, which must be completed within 60 days of receiving the denial.[disability-benefits-help.org]
Delayed Milestone
  • Bahrain Al-Mukharraq (1997) described a 49-month-old Bahraini boy who presented at the age of six months with history of upper respiratory tract infection, pallor, generalized lymphadenopathy, hepatosplenomegaly, and delayed milestones.[cags.org.ae]

Workup

  • When a young patient presents with cotton wool spots, a thorough workup must be done, and immunologic disorders should be considered in the differential diagnosis.[ncbi.nlm.nih.gov]
Hypertriglyceridemia
  • ., fever, splenomegaly, cytopenia, and hypertriglyceridemia), the family history, his B-cell lymphoma, and hypogammaglobulinemia pointed toward XLP.[thieme-connect.com]
Enlargement of the Liver
  • liver and spleen, and lymphoma.[chop.edu]
  • […] of the liver and/or spleen • Muscle aches and pains Since the immune system of individuals with Epstein-Barr virus (EBV) does not function properly in response to the virus, potentially severe complications can develop such as: • Hepatitis (inflammation[checkorphan.org]
  • […] of the liver (hepatomegaly), and/or abnormal functioning of the liver, resulting in yellowing of the skin, mucous membranes, and whites of the eyes (jaundice or icterus).[lymphedemapeople.com]
Streptococcus Pneumoniae
  • The blood and CSF cultures grew Streptococcus pneumonia. Saudi Arabia Alangari et al. (2006) described a 7-year old Saudi boy with XLP and growth hormone deficiency. The patients had a history of recurrent infections and growth failure.[cags.org.ae]
Ischemic Changes
  • Eye pathologic examination at autopsy showed ischemic changes, but no inflammation. When a young patient presents with cotton wool spots, a thorough workup must be done, and immunologic disorders should be considered in the differential diagnosis.[ncbi.nlm.nih.gov]

Treatment

  • […] stem cell transplant (HSCT). [5] However, depending on clinical features, less aggressive treatments may be adopted, particularly if a suitable donor for transplant is not available.[emedicine.medscape.com]
  • Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions .[patient.info]
  • There are several treatment options available for those with the disorder.[disability-benefits-help.org]
  • Source: Children's Hospital of Philadelphia Treatment - X-linked lymphoproliferative syndrome Regardless of clinical phenotype, the only curative treatment is allogeneic hematopoietic cell transplantation (HCT), which should be considered in all patients[checkorphan.org]
  • Supportive treatment is recommended by antibiotics, that prevent other infections, and by immunoglobulin supplements, however, bone marrow transplantation remains the best choice of treatment. About 70% of untreated cases die by the age of 10 years.[cags.org.ae]

Prognosis

  • X-linked lymphoproliferative disorder typically presents as an Epstein-Barr virus-specific immune defect with a poor prognosis.[ncbi.nlm.nih.gov]
  • XLP is a disease with a poor prognosis. Over 70% of patients die by the age of 10 due to fatal infectious mononucleosis.[jstage.jst.go.jp]
  • Prognosis for those patients has dramatically improved over the decades due to improved lymphoma chemotherapy protocols. [6] Jin YY, Zhou W, Tian ZQ, Chen TX.[emedicine.medscape.com]
  • If one of these tests reveals that the baby is a boy, DNA from his fetal cells can be analyzed for presence or absence of the SH2D1A mutation Source: Children's Hospital of Philadelphia Prognosis - X-linked lymphoproliferative syndrome What are the cancer[checkorphan.org]

Etiology

  • Therefore the defect in XLP converts normally activating signals into inhibitory signals. [7, 8, 9, 10] An XLP syndrome caused by mutations in the inhibitor-of-apoptosis gene XIAP has also been reported. [11, 12] Etiology Mutations in the SH2D1A and XIAP[emedicine.medscape.com]
  • […] lymphoproliferative disorder (XLP, Duncan syndrome) Nijmegen breakage syndrome (NBS) Hyper IgM syndrome Autoimmune lymphoproliferative syndrome (ALPS, Canale-Smith syndrome) Sites Dependent on the underlying disease Most commonly extranodal: GI tract, lung, CNS Etiology[pathologyoutlines.com]
  • Intracranial aneurysm etiologies include atherosclerosis, hypertension, vasculopathy, trauma, drug abuse, neoplasm, and infection.[ajnr.org]

Epidemiology

  • SH2D1A gene mutations cause XLP1, and XIAP gene mutations cause XLP2. [13] Epidemiology X-linked lymphoproliferative (XLP) syndrome is rare. XLP1 is estimated to occur in about 1 in 1,000,000 males worldwide.[emedicine.medscape.com]
  • […] deficiency due to a primary immunodeficiency or immunoregulatory disorder ( WHO ) Usually extranodal Varies from polymorphous proliferation of lymphoid cells to diverse lymphomas Usually humoral (B cell) types but also cellular (T cell) types Usually EBV Epidemiology[pathologyoutlines.com]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology X-linked lymphoproliferative (XLP) syndrome is characterized by a high susceptibility to severe infection with EBV. Hemophagocytic lymphohistiocytosis is the most common presenting feature.[emedicine.medscape.com]
  • The substantial progress in understanding the XLP pathophysiology was made with revealing the molecular basis of this immunodeficiency.[exp-oncology.com.ua]
  • Pathophysiology: In XLP syndrome, the most striking manifestation is that EBV triggers an initial episode of IM that causes death, usually by liver failure secondary to hepatic necrosis, in more than 50% of infected children.[lymphedemapeople.com]

Prevention

  • This mutation causes reduced levels of XIAP and may prevent the immune system from controlling the viral infection.[sparks.org.uk]
  • Rituximab can help prevent severe EBV infection before transplantation. Drug Name Select Trade Rituximab RITUXAN Click here for Patient Education NOTE: This is the Professional Version.[merckmanuals.com]
  • Supportive treatment is recommended by antibiotics, that prevent other infections, and by immunoglobulin supplements, however, bone marrow transplantation remains the best choice of treatment. About 70% of untreated cases die by the age of 10 years.[cags.org.ae]
  • Most of the time, the immune system does a great job of keeping people healthy and preventing infections.[chop.edu]

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