Purtilo syndromeD82.3
Synonym(s)
HistoryThis section has been translated automatically.
The name "Purtilo syndrome" refers to the author of the initial 1974 description D. T. Purtilo. Duncan is the name of the described family.
DefinitionThis section has been translated automatically.
X-linked lymphoproliferative syndrome (XLP) is a rare, x-linked, recessively inherited primary immunodeficiency. It is caused by mutations of genes on the X chromosome.
ClassificationThis section has been translated automatically.
X-linked lymphoproliferative syndrome type 1 is the most common type (about 60% of all cases) is caused by a mutation in the SH2D1A gene at location Xq25. This gene encodes the signaling lymphocyte activation molecule (SLAM)-associated protein (SAP, also referred to as SH2 domain protein 1A or DSHP). Without SAP, lymphocytes proliferate in an uncontrolled response to Epstein-Barr virus(EBV/HHV-4) infection, while natural killer (NK) cells are deficient in function.
X-linked lymphoproliferative syndrome type 2 is phenotypically similar to type 1; it predisposes to hemophagocytic lymphohistiocytosis(HLH). XLP2 is caused by mutations in a gene also located on Xq25 that encodes the X-linked inhibitor of apoptosis protein(XIAP gene).
Occurrence/EpidemiologyThis section has been translated automatically.
Incidence: <1/ 100.000 persons
EtiopathogenesisThis section has been translated automatically.
On the one hand, the defective SAP protein leads to the activation of certain cell functions being impaired. For example, natural killer (NK) cells or cytotoxic T cells can only insufficiently perform one of their essential tasks, the killing of virus-infected cells. Their task of supporting B lymphocytes in the formation of antibodies is also impaired.
Mutations of the 2nd gene(XIAP gene) also lead to XLP. This gene is also located on the X chromosome and codes for a protein involved in triggering apoptosis of immune cells.
ManifestationThis section has been translated automatically.
Disease onset in early infancy (2 to 3 years of age), after infection with the Epstein-Barr virus (HHV-4).
Infectious mononucleosis leads to mostly harmless, flu-like symptoms in immunocompromised children. In XLP disease, it leads to a highly acute and often life-threatening Epstein-Barr virus infection (Gilmour KC et al. 2000).
Clinical featuresThis section has been translated automatically.
Primary phase of the disease: severe sore throat, fatigue and exhaustion, accompanied by loss of appetite, headache and fever. The tonsils are covered with grayish dirty coatings. A transient skin rash is often seen. In the course, there is generalized lymphadenopathy, hepato- and splenomegaly.
Postinfectious: After a more or less severe course of infectious mononucleosis, XLP usually presents in school-age children as a secondary antibody deficiency syndrome, with a CVID (common variable immunodeficiency) like clinical picture. The consequence is frequent infections.
bacterial infections of the respiratory tract:
- Middle ear infections
- sinus infections
- bronchitis
- pneumonias
viral infections:
- e.g. herpes simplex infections
fungal infections:
- e.g. oral thrush or onychomycosis.
Chronic diarrheal diseases are more common.
Rarer signs of disease observed in XLP patients (3-5% of all patients) are:
- aplastic anemia
- vasculitis
- granulomatous changes in different organs
- bronchiectasis of the lung
LaboratoryThis section has been translated automatically.
Thrombocytopenia with the danger of an increased bleeding tendency. Many of the affected children develop a life-threatening haemophagocytosis syndrome (HLH) during the course of the disease, which leads to the destruction of the body's own blood cells and to a highly inflammatory disease of many organs.
Complication(s)This section has been translated automatically.
hepatitis, myocarditis, encephalitis, nephritis, or pneumonia; B-cell lymphomas ( Woon ST et al. 2008)
TherapyThis section has been translated automatically.
The treatment of XLP consists in the transplantation of hematopoietic stem cells.
Unless haematopoietic stem cell transplantation is performed, about 75% of patients do not reach the age of 10 years! All patients die before the age of 40.
About 80% of patients who receive a transplant survive.
A transplant is curative if it is performed before Epstein-Barr virus infection or other disorders have induced irreversible damage.
Note(s)This section has been translated automatically.
A tentative diagnosis should be made in the case of:
decreased antibody responses to antigens (especially EBV nuclear antigen)
impaired T cell proliferative response to mitogens
decreased NK cell function
an inverted CD4: CD8 ratio
These findings are typical before and after Epstein-Barr virus infection . Bone marrow biopsy may help confirm HLH.
Note: Genetic testing of relatives is performed when a case or carrier has been identified in a family. Prenatal screening is recommended in individuals in whom a mutation causing XLP has been identified in the family.
LiteratureThis section has been translated automatically.
- Gilmour KC et al (2000) Diagnosis of X-linked lymphoproliferative disease by analysis of SLAM-associated protein expression. Eur J Immunol 30:1691-1697.
- Lyu X et al (2018) Identification of a novel nonsense mutation in SH2D1A in a patient with X-linked lymphoproliferative syndrome type 1: a case report. BMC Med Genet 19:60.
- Purtilo DT et al (1974) Letter: Fatal infectious mononucleosis in familial lymphohistiocytosis. New Engl J Med 291: 736
- Skare JC et al (1987) Mapping the X-linked lymphoproliferative syndrome. Proc Natl Acad Sci U S A 84:2015-2018.
- Woon ST et al (2008) Follicular lymphoma in a X-linked lymphoproliferative syndrome 1carrier female. Scand J Immunol 68:153-158.