X-LINKED LYMPHOPROLIFERATIVE DISEASE

Duncan Syndrome; Duncan Disease; Epstein-Barr Virus-Induced Lymphoproliferative Disease in Males; Immunodeficiency-5 (IMD5); EBV Susceptibility (EBVS); Purtilo syndrome

X-Linked Lymphoproliferative Disease (XLD) is an immune system disorder that is found almost exclusively in males. Individuals with XLD have an increased risk of infection because their body cannot properly regulate the number of immune system cells (lymphocytes) and blood cells.  People have two main types of lymphocytes, B cells and T cells, which work together to clear infections and keep the immune system in check. Individuals with XLD lack the proper regulation between B cells and T cells and are therefore unable to affectively destroy invading viruses, such as the usually harmless Epstein-Barr virus (EBV). Typically, individuals with XLD do not display severe symptoms of a compromised immune system until they have been exposed to EBV. EBV infections, however, are common and can become life-threatening in people with XLD resulting in symptoms that include fever, hepatitis, an enlarged spleen, abnormally low numbers of antibodies, and, in some cases, lymphoma and other blood disorders.  XLD is caused by mutations in the SH2D1A gene which makes a protein SAP, a key regulator in immunity, as well as the XIAP gene. XLD is inherited in an X-linked recessive pattern.

Diagnostic testing: A definitive diagnosis of XLD is based on:

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  Genetic analysis for mutations in the SH2D1A gene and XIAP gene;

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  CT or MRI scans of the liver and spleen showing abnormal enlargement;

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  Laboratory testing showing abnormally high concentrations of lymphocytes in the blood (lymphocytosis);

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  Laboratory tests showing deficient or absent antibody response to EBV antigens (e.g., EBV nuclear antigen);

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  Laboratory tests showing abnormally low levels of all classes of immunoglobulins (acquired hypogammaglobulinemia) in the blood and body secretions.

Physical findings: Findings may include:

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  Infectious mononucleosis;

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  Dysgammaglobunemia;

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  Lymphoid granulomatosis of the lungs;

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  Hepatomegaly;

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  Fulminant hepatitis;

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  Liver failure;

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  Splenomegaly;

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  Meningitis or encephalitis;

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  Malignant lymphoma;

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  Aplastic anemia;

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  Thrombocytopenia or bone marrow failure; and

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  Vasculitis.

ICD-9: 238.79

XLD is generally diagnosed between the ages of six months to 10 years of age when the initial symptoms of XLD become evident. The prognosis of XLD depends on the occurrence of complications, such as lymphomas and hemophagocytic lymphohistiocytosis. Without allogenic (donor) bone marrow transplantation, approximately 70% of individuals with XLD may not survive beyond the age of 10 years.

Treatment of XLD may include anti-viral medicines, immunoglobulin therapy or corticosteroids, chemotherapy or antithymocyte globulin. The definitive treatment for XLD is transplantation. XLD affects multiple functions in the body requiring the coordination of care by pediatricians, immunologists, hematologists, oncologists, and other health care professionals.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

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  Clinical history and examination that describes diagnostic features of the impairment;

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  Imaging tests including CT scans and MRI;

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  Laboratory testing of the blood; and

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  Biopsy reports.

Suggested Listings for Evaluation:

REMARKS

Listing level malignant neoplastic (for example, lymphoma) and/or immunodeficiency findings must be documented; diagnosis or laboratory testing results alone will not meet listing severity.