Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2001 Oct;126(1):126-30.
doi: 10.1046/j.1365-2249.2001.01599.x.

X-linked lymphoproliferative disease: three atypical cases

K Nistala  1 , K C Gilmour, T Cranston, E G Davies, D Goldblatt, H B Gaspar, A M Jones
Affiliations
Case Reports

X-linked lymphoproliferative disease: three atypical cases

K Nistala et al. Clin Exp Immunol. 2001 Oct.

Abstract

Common variable immunodeficiency (CVID) is the most frequently occurring primary immunodeficiency in both children and adults. The molecular basis of CVID has not been defined, and diagnosis involves exclusion of other molecularly defined disorders. X-linked lymphoproliferative disease (XLP) is a rare disorder in which severe immunodysregulatory phenomena typically follow Epstein-Barr virus (EBV) infection. Boys who survive initial EBV infection have a high incidence of severe complications, including progressive immunodeficiency, aplastic anaemia, lymphoproliferative disease and lymphoma. Survival beyond the second decade is unusual, although bone marrow transplantation can be curative. Until recently reliable diagnostic testing for XLP has not been available, but the identification of the XLP gene, known as SH2D1A, and coding for a protein known as SAP, means that molecular diagnosis is now possible, both by protein expression assays, and mutation detection, although the mutation detection rate in several series is only 55-60%. We describe three male patients initially diagnosed as affected by CVID, one of whom developed fatal complications suggestive of XLP, and all of whom lack expression of SAP. Two out of three have disease-causing mutations in the SAP gene, consistent with published data for XLP. These findings raise the possibility that a subgroup of patients with CVID may be phenotypic variants of XLP. Further studies are necessary to investigate this possibility, and also to clarify the prognostic significance of SAP abnormalities in such patients in the absence of typical features of XLP.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Western blot analysis of SAP expression in Case 1, 2 and 3. C: normal control; P1: Case 1; P2: Case 2; P3: Case 3. The SAP specific band is absent in all three affected boys. Normal actin specific bands are present in all affected boys and controls.
Fig. 2
Fig. 2
Sequencing data from Cases 1(a) and 2 (b). In Case 1 a single nucleotide substitution results in a single amino acid alteration (Glycine to Valine, G39V). In Case 2 a 5-bp intronic deletion (IVS3 − 28 to − 32 del ATTTT) probably leads to transcription of an unstable mRNA.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) Clin Immunol. 1999;93:190–7. - PubMed
    1. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48. 10.1006/clim.1999.4725. - DOI - PubMed
    1. Kanegane H, Tsukada S, Iwata T, et al. Detection of Bruton's tyrosine kinase mutations in hypogammaglobulinaemic males registered as common variable immunodeficiency (CVID) in the Japanese Immunodeficiency Registry. Clin Exp Immunol. 2000;120:512–7. 10.1046/j.1365-2249.2000.01244.x. - DOI - PMC - PubMed
    1. Vorechovsky I, Cullen M, Carrington M, Hammarstrom L, Webster AD. Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: identification and characterization of haplotypes shared by affected members of 101 multiple-case families. J Immunol. 2000;164:4408–16. - PubMed
    1. Purtilo DT, Cassel CK, Yang JP, Harper R. X-linked recessive progressive combined variable immunodeficiency (Duncan's disease) Lancet. 1975;1:935–40. - PubMed

Publication types

MeSH terms

Substances