X-linked lymphoproliferative disease

X-linked lymphoproliferative disease
[[File:|250px|alt=|]]
Synonyms
Pronounce
Field
Symptoms
Complications
Onset
Duration
Types
Causes
Risks
Diagnosis
Differential diagnosis
Prevention
Treatment
Medication
Prognosis
Frequency
Deaths

X-linked lymphoproliferative disease (also known as "Duncan's disease"<ref name="Andrews">{{{last}}},

 James, William D., 
  
 Andrews' Diseases of the Skin: clinical Dermatology, 
  
 Saunders Elsevier, 
 2006, 
  
  
 ISBN 0-7216-2921-0,</ref>  or "Purtilo syndrome"<ref>http://ghr.nlm.nih.gov/condition/x-linked-lymphoproliferative-disease</ref>) is a lymphoproliferative disorder.<ref name="Bolognia">{{{last}}}, 
 Rapini, Ronald P., 
  
 Dermatology: 2-Volume Set, 
  
 St. Louis:Mosby, 
 2007, 
  
  
 ISBN 1-4160-2999-0, 
  
  
  
 Pages: 808,</ref>

Presentation

Strangely, in boys with X-linked lymphoproliferative disorder, there is an inability to mount an immune response to the Epstein-Barr virus (EBV),<ref name="Robbins">{{{last}}},

 Kumar, Vinay, 
  
 Robbins Basic Pathology, 
 7th edition, 
 Philadelphia:Elsevier, 
 2003, 
  
  
 ISBN 1-4160-2534-0, 
  
  
  
 Pages: 418,</ref> which often leads to death from bone marrow failure, irreversible hepatitis, and malignant lymphoma. However, the connection between EBV and X-linked lymphoproliferative disorder is yet to be determined.<ref name="item14">Lymphoproliferative Disorders at eMedicine

</ref>

Patients produce insufficient numbers of CD27 memory B cells.<ref name="pmid16424938">,

 Selective generation of functional somatically mutated IgM+CD27+, but not Ig isotype-switched, memory B cells in X-linked lymphoproliferative disease, 
 J. Clin. Invest., 
 
 Vol. 116(Issue: 2),
 pp. 322–33,
 DOI: 10.1172/JCI25720,
 PMID: 16424938,
 PMC: 1332028,</ref>

Cause

XLP1

There is a mutation on the X-chromosome that has been found to be associated with a T- and NK-cell lymphoproliferative disorder. The mutation is on the long arm of the chromosome, at position 25, which is denoted as Xq25. At this position, there is a deletion in the SH2D1A gene, which codes for an SH2 domain on a signal transducing protein called SLAM-associated protein (SAP).

The term "SH2" domain stands for src-homology 2 domain, which is a three-dimensional domain structure of about 100 amino acid residues. These domains are present in many signalling proteins because they permit specific, non-covalent bonding to proteins that contain phosphotyrosines. The amino acid residues adjacent to the phosphotyrosine on the target protein are what determine the unique binding specificity.<ref name="item1">{{{last}}},

 Abbas, A.K, 
  
 Cellular and Molecular Immunology, 
 5th edition, 
 Philadelphia:Elsevier Saunders, 
 2005,</ref>

The SAP protein is important in the signalling events that activate T- and NK-cells<ref name="titleX-linked Lymphoproliferative Syndrome: Immunodeficiency Disorders: Merck Manual Professional">Template:MerckManual</ref> due to its adaptor function. Normally, the SAP protein is expressed in the cytoplasm of T- and NK-cells, where it binds to the cytoplasmic domain of the surface receptor called signaling lymphocyte activation molecule (SLAM). This binding initiates a signal transduction pathway, which results in the modulation of IFN-γ. A deletion in the SH2D1A gene leads to a non-functional SH2 domain on the SAP protein, making it unable to bind to SLAM. This leads to aberrant IFN-γ modulation, causing uncontrolled cell proliferation.

XLP2

A second form is associated with XIAP.<ref>,

 XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome, 
 Nature, 
 
 Vol. 444(Issue: 7115),
 pp. 110–4,
 DOI: 10.1038/nature05257,
 PMID: 17080092,</ref>

Some sources recommend classifying this condition as "X-linked familial hemophagocytic lymphohistiocytosis" instead of X-linked lymphoproliferative disease.<ref name="pmid20489057">,

 XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease, 
 Blood, 
 
 Vol. 116(Issue: 7),
 pp. 1079–82,
 DOI: 10.1182/blood-2010-01-256099,
 PMID: 20489057,
 PMC: 2938130,</ref>

Eponym

It is also known as Duncan Disease, after 6 of 18 males in the Duncan family died of lymphoproliferative disease, including fulminant infectious mononucleosis and lymphoma <ref>1.Purtilo DT, Cassel C, Yang JP. Letter: Fatal infectious mononucleosis in familial lymphohistiocytosis. N Engl J Med 1974; 291:736.</ref>. It is also called "Purtilo's Syndrome", after Dr. David Theodore Purtilo (1939–1992), a pioneering Pathologist and Immunologist at the American Army Center for Pathology in Washington, who discovered it in the early 1970s. A native of Duluth, Minnesota, he pioneered the research for this condition after discovering it in one of his patients. In the late 1980s, he resided in Omaha, Nebraska and died on September 28, 1992 in Florida, after suffering a stroke before he could deliver a speech to a forum.<ref>https://www.nytimes.com/1992/10/03/us/david-t-purtilo-53-a-specialist-in-disorders-of-the-immune-system.html</ref>

External links

• GeneReview/NIH/UW entry on Lymphoproliferative Disease, X-Linked

This article is a stub. You can help WikiMD by registering to expand it. Editing is available only to registered and verified users. WikiMD is a comprehensive, free health & wellness encyclopedia.