Abstract
X-linked lymphoproliferative disease is a rare immunodeficiency disorder characterized by extreme vulnerability to Epstein-Barr virus, dysgammaglobulinemia, and very high incidence of lymphoma. Growth-hormone deficiency has been described in rare cases to be associated with certain immunodeficiencies, such as X-linked agammaglobulinemia. We report a first case with X-linked lymphoproliferative disease associated with hypogammaglobulinemia and growth-hormone deficiency, which was confirmed by SAP gene mutation. The patient’s mutation is novel. He is also the first patient with X-linked lymphoproliferative disease to be reported from Saudi Arabia. The patient’s Btk expression and BTK gene were normal. Patients with hypogammaglobulinemia and GH deficiency should be considered to have not only X-linked agammaglobulinemia, but also X-linked lymphoproliferative disease.
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Abbreviations
- XLP:
-
X-linked lymphoproliferative disease
- XLA:
-
X-linked agammaglobulinemia
- BTK:
-
Bruton tyrosine kinase
- GH:
-
Growth hormone
- SAP:
-
SLAM (signaling lymphocyte activating molecule)-associated protein
- EBV:
-
Epstein-Barr virus
References
Agamohammadi A, Kanegane H, Moein M, Farhoudi A, Pourpak Z, Movahedi M, Gharagozlou M, Zargar A, Miyawaki T (2003) Identification of an SH2D1A mutation in a hypogammaglobulinemic male patient with a diagnosis of common variable immunodeficiency. Int J Hematol 78:45-47
Buzi F, Notarangelo LD, Plebani A, Duse M, Parolini O, Monteleone M, Ugazio AG (1994) X-linked agammaglobulinemia, growth hormone deficiency and delay of growth and puberty. Acta Paediatr 83:99–102
Conley ME, Burks AW, Herrod HG, Puck JM (1991) Molecular analysis of X-linked agammaglobulinemia with growth hormone deficiency. J Pediatr 119:392–397
Duriez B, Duquesnoy P, Dastot F, Bougneres P, Amselem S, Goossens M (1994) An exon-skipping mutation in the btk gene of a patient with X-linked agammaglobulinemia and isolated growth hormone deficiency. FEBS Letters 346:165–170
Fleisher TA, White RM, Broder S, Nissley P, Blaese RM, Mulvihill JJ, Olive G (1980) Waldmann T. X-linked hypogammaglobulinemia and isolated growth hormone deficiency. N Engl J Med 302:1429–1434
Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J, Pratt KL, Bezrodnik L, Jasper H, Tepper A, Heinrich J, Rosenfeld RG (2003) Growth hormone insensitivity associated with a STAT5b mutation. N Eng J Med 349:1139–1147
Kornfeld SJ, Kratz J, Diamond F, Day N, Good RA (1995) Shwachman-Diamond syndrome associated with hypogammaglobulinemia and growth hormone deficiency. J Allergy Clin Immunol 96:247–250
Nichols KE, Ma CS, Cannons JL, Schwartzberg PL, Tangye SG (2005) Molecular and cellular pathogenesis of X-linked lymphoproliferative disease. Immunol Rev 203:180–199
Ohezki T, Hanaki K, Motozumi H, Ohtahara H, Hayashibara H, Harada Y, Shikari K, Tsuji Y, Emura H (1993) Immunodeficiency with increased immunoglobulin M associated with growth hormone deficiency. Acta Paediatr 82:620–623
Shinozaki K, Kanegane H, Matsukura H, Sumazaki R, Tsuchida M, Makita M, Kimoto Y, Kanai R, Tsumura K, Kondoh T, Moriuchi H, Miyawaki T (2002) Activation-dependent T cell expression of the X-linked lymphoproliferative disease gene product SLAM-associated protein and its assessment for patient detection. Int Immunol 14:1215–1223
Stewart DM, Notarangelo LD, Kurman CC, Staudt LM, Nelson DL (1995) Molecular genetic analysis of X-linked hypogammaglobulinemia and isolated growth hormone deficiency. J Immunol 155:2770–2774
Sumegi J, Huang D, Lanyi A, Davis JD, Seemayer TA, Maeda A, Klein G, Seri M, Wakiguchi H, Purtilo D, Gross T (2000) Correlation of mutations of the SH2D1A gene and Epstein-Barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease. Blood 96:3118–3125
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This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Ministry of Health, Labour, and Welfare of Japan. The authors declare no potential conflict of interest, real or perceived.
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Alangari, A., Abobaker, A., Kanegane, H. et al. X-linked lymphoproliferative disease associated with hypogammaglobulinemia and growth-hormone deficiency. Eur J Pediatr 165, 165–167 (2006). https://doi.org/10.1007/s00431-005-0023-x
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DOI: https://doi.org/10.1007/s00431-005-0023-x