Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021345 (infectious mononucleosis)
 3,358 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked lymphoproliferative (XLP) syndrome is a rare primary immune-deficiency disorder caused by mutations of the SH2D1A or XIAP genes. Males with the disorder are usually in good health until contracting Epstein-Barr virus (EBV) whereupon the majority of patients die from fulminant infectious mononucleosis, lymphoma or hypogammaglobulinaemia. This report describes a female carrier with an XLP phenotype who was retrospectively identified after her grandson died from the disorder. Subsequent genetic testing identified the patient's mother and affected maternal grandmother as XLP carriers. The family's medical records were significant. The proband had lymphoma at ages 2 and 8 and made a full recovery following treatment. Both the maternal grandmother and uncle died of non-Hodgkin's lymphoma. We were concerned that the XLP carrier mother may be predisposed to lymphoma if the normal X chromosome is skewed towards inactivation. The human androgen receptor assay detected random X chromosome inactivation in the carrier mother. EBV was not detected in the lymphoma tissues of the proband and his grandmother, confirming previous findings that EBV is not always associated with lymphoma in XLP. More significantly, our study highlights the importance of identifying XLP in families with a high incidence of lymphoma.
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PMID:Follicular lymphoma in a X-linked lymphoproliferative syndrome carrier female. 1870 45

X-linked lymphoproliferative disease is a rare congenital immunodeficiency that is most often caused by mutations in SH2D1A, the gene encoding signaling lymphocyte activation molecule (SLAM)-associated protein (SAP). XLP caused by SAP deficiency is most often characterized by fulminant mononucleosis/EBV- associated hemophagocytic lymphohistiocytosis (HLH), lymphoma, and dysgammaglobulinemia. XLP has also been found to be caused by mutations in BIRC4, the gene encoding X-linked inhibitor of apoptosis (XIAP). Patients with XIAP deficiency often present with HLH or recurrent HLH, which may or may not be associated with EBV. XLP is prematurely lethal in the majority of cases. While genetic sequencing can provide a genetic diagnosis of XLP, a more rapid means of diagnosis of XLP is desirable. Rapid diagnosis is especially important in the setting of HLH, as this may hasten the initiation of life-saving medical treatments and expedite preparations for allogeneic hematopoietic cell transplantation (HCT). Flow cytometry offers a means to quickly screen patients for XLP. Flow cytometry can be used to measure lymphocyte SAP or XIAP protein expression, and can also be used to observe lymphocyte phenotypes and functional defects that are unique to XLP. This review will give a brief overview of the clinical manifestations and molecular basis of SAP deficiency and XIAP deficiency, and will focus on the use of flow cytometry for diagnosis of XLP.
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PMID:Using flow cytometry to screen patients for X-linked lymphoproliferative disease due to SAP deficiency and XIAP deficiency. 2081 73

In this study, we report the clinical and genetic features of Chinese patients with X-linked lymphoproliferative syndrome (XLP). Male patients with fulminant infectious mononucleosis (FIM), Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) or persistent EBV viremia were enrolled in this study. Direct sequencing was used to detect SH2D1A/XIAP gene mutations. The patients' clinical features were assessed by retrieval of data from medical records. Twenty-one male patients with FIM, EBV-associated HLH or persistent EBV viremia were evaluated. Four patients had SH2D1A mutations, and one patient had an XIAP mutation. All five of these patients had symptoms of HLH and EBV infection. Among the five patients, the youngest one was only 1 month old at onset. One patient exhibited hypogammaglobulinemia. Of four patients evaluated for immunological function, all exhibited reduced CD4/CD8 ratios. Three patients had rapid disease progression and died. One patient received haematopoietic stem cell transplantation and is well. The overall clinical phenotypes of Chinese patients with XLP matched previous reports. For patients with severe EBV-associated HLH, our results indicate the need to examine the possibility of XLP.
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PMID:Clinical and genetic features of 5 Chinese patients with X-linked lymphoproliferative syndrome. 2394 11

X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant clinical phenotype. Among 25 symptomatic patients diagnosed with XIAP deficiency, we identified 17 patients who initially presented with manifestations other than HLH. These included Crohn-like bowel disease (n=6), severe infectious mononucleosis (n=4), isolated splenomegaly (n=3), uveitis (n=1), periodic fever (n=1), fistulating skin abscesses (n=1) and severe Giardia enteritis (n=1). Subsequent manifestations included celiac-like disease, antibody deficiency, splenomegaly and partial HLH. Screening by flow cytometry identified 14 of 17 patients in our cohort. However, neither genotype nor protein expression nor results from cell death studies were clearly associated with the clinical phenotype. Only mutation analysis can reliably identify affected patients. XIAP deficiency must be considered in a wide range of clinical presentations.
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PMID:X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis. 2397 92

Primary immunodeficiencies with selective susceptibility to EBV infection are rare conditions associated with severe lymphoproliferation. We followed a patient, son of consanguineous parents, referred to our center for recurrent periodic episodes of fever associated with tonsillitis and adenitis started after an infectious mononucleosis and responsive to oral steroid. An initial diagnosis of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome was done. In the following months, recurrent respiratory infections and episodes of keratitis were also observed, together with a progressive reduction of immunoglobulin levels and an increase of CD20+ cells. Cell sorting and EBV PCR showed 25,000 copies for 100,000 leukocytes with predominant infection of B lymphocytes. Lymph node's biopsy revealed reactive lymphadenopathy with paracortical involvement consistent with a chronic EBV infection. Molecular analysis of XIAP, SHA2D1A, ITK, and CD27 genes did not detect any pathogenic mutation. The patients underwent repeated courses of anti-CD20 therapy with only a partial control of the disease, followed by stem cell transplantation with a complete normalization of clinical and immunological features. Whole exome sequencing of the trio was performed. Among the variants identified, a novel loss of function homozygous c.163-2A>G mutation of the CD70 gene, affecting the exon 2 AG-acceptor splice site, fit the expected recessive model of inheritance. Indeed, deficiency of both CD27, and, more recently, of its ligand CD70, has been reported as a cause of EBV-driven lymphoproliferation and hypogammaglobulinemia. Cell surface analysis of patient-derived PHA-T cell blasts and EBV-transformed lymphoblastoid cell lines confirmed absence of CD70 expression. In conclusion, we describe a case of severe chronic EBV infection caused by a novel mutation of CD70 presenting with recurrent periodic fever.
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PMID:CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic Fever. 2943 83