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Open Access 01-12-2014 | Research article

Clinical and mutational features of Vietnamese children with X-linked agammaglobulinemia

Authors: Quang Van Vu, Taizo Wada, Huong Thi Minh Le, Hai Thanh Le, Anh Thi Van Nguyen, Ohara Osamu, Akihiro Yachie, Sang Ngoc Nguyen

Published in: BMC Pediatrics | Issue 1/2014

Abstract

Background

X-linked agammaglobulinemia (XLA) is a primary immune deficiency characterized by recurrent bacterial infections and profoundly depressed serum immunoglobulin levels and circulating mature B cells. It is caused by mutations of the Bruton tyrosine kinase (BTK) gene and is the most common form of inherited antibody deficiency. To our knowledge, this is the first report of XLA from Vietnam.

Methods

We investigated the BTK gene mutations and clinical features of four unrelated Vietnamese children.

Results

The mean ages at onset and at diagnosis were 2.5 and 8 years, respectively. All patients had a medical history of otitis media, pneumonia, and septicemia at the time of diagnosis. Other infections reported included sinusitis, bronchiectasis, arthritis, skin infections, meningitis, and recurrent diarrhea. We identified one previously reported mutation (c.441G >A) and three novel mutations: two frameshifts (c.1770delG and c.1742 delG), and one nonsense (c.1249A >T).

Conclusions

The delayed diagnosis may be attributable to insufficient awareness of this rare disease on the background of frequent infections even in the immunocompetent pediatric population in Vietnam. Our results further support the importance of molecular genetic testing in diagnosis of XLA.

Bruton OC: Agammaglobulinemia. Pediatrics. 1952, 9: 722-728.PubMed

Velickovic M, Prasad ML, Weston SA, Benson EM: Identification of the bruton tyrosine kinase (BTK) gene mutations in 20 Australian families with X-linked agammaglobulinemia (XLA). Hum Mutat. 2004, 23: 398-399.CrossRefPubMed

Kristufek D, Aspalter RM, Eibl MM, Wolf HM: Characterization of novel Bruton’s tyrosine kinase gene mutations in central European patients with agammaglobulinemia. Mol Immunol. 2007, 44: 1639-1643. 10.1016/j.molimm.2006.08.003.CrossRefPubMed

Fiorini M, Franceschini R, Soresina A, Schumacher R-F, Ugazio AG, Rossi P, Plebani A, Notarangelo LD: BTK: 22 novel and 25 recurrent mutations in European patients with X-linked agammaglobulinemia. Hum Mutat. 2004, 23: 286-CrossRefPubMed

Zhang Z-Y, Zhao X-D, Jiang L-P, Liu E-M, Wang M, Yu J, Liu P, Yang X-Q: Clinical characteristics and molecular analysis of 21 Chinese children with congenital agammaglobulinemia. Scand J Immunol. 2010, 72: 454-459. 10.1111/j.1365-3083.2010.02457.x.CrossRefPubMed

Shin D-M, Jo E-K, Kanegane H, Futatani T, Zhao M, Song C-H, Yamagishi A, Miyawaki T: Transcriptional regulatory defects in the first intron of Bruton’s tyrosine kinase. Pediatr Int. 2008, 50: 801-805. 10.1111/j.1442-200X.2008.02739.x.CrossRefPubMed

Shinomiya N, Kanegane H, Watanabe A, Yamaguchi Y, Futatani T, Miyawaki T: Point mutation in intron 11 of Bruton’s tyrosine kinase in atypical X-linked agammaglobulinemia. Pediatr Int. 2000, 42: 689-692. 10.1046/j.1442-200x.2000.01293.x.CrossRefPubMed

Wang Y, Kanegane H, Wang X, Han X, Zhang Q, Zhao S, Yu Y, Wang J, Miyawaki T: Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China. J Clin Immunol. 2009, 29: 352-356. 10.1007/s10875-008-9262-8.CrossRefPubMed

Futatani T, Miyawaki T, Tsukada S, Hashimoto S, Kunikata T, Arai S, Kurimoto M, Niida Y, Matsuoka H, Sakiyama Y, Iwata T, Tsuchiya S, Tatsuzawa O, Yoshizaki K, Kishimoto T: Deficient expression of Bruton’s tyrosine kinase in monocytes from X-linked agammaglobulinemia as evaluated by a flow cytometric analysis and its clinical application to carrier detection. Blood. 1998, 91: 595-602.PubMed

10.

Trakultivakorn M, Ochs HD: X-linked agammaglobulinemia in northern Thailand. Asian Pac J Allergy Immunol. 2006, 24: 57-63.PubMed

11.

Noh LM, Ismail Z, Zainudin BM, Low SM, Azizi BH, Noah RM, Nasaruddin BA: Clinical patterns of X linked agammaglobulinemia in Malaysian children. Acta Paediatr Jpn. 1995, 37: 331-335. 10.1111/j.1442-200X.1995.tb03324.x.CrossRefPubMed

12.

Vetrie D, Vorechovský I, Sideras P, Holland J, Davies A, Flinter F, Hammarström L, Kinnon C, Levinsky R, Bobrow M: The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. 1993, 361: 226-233. 10.1038/361226a0.CrossRefPubMed

13.

Conley ME, Broides A, Hernandez-Trujillo V, Howard V, Kanegane H, Miyawaki T, Shurtleff SA: Genetic analysis of patients with defects in early B-cell development. Immunol Rev. 2005, 203: 216-234. 10.1111/j.0105-2896.2005.00233.x.CrossRefPubMed

14.

Lindvall JM, Blomberg KEM, Valiaho J, Vargas L, Heinonen JE, Berglof A, Mohamed AJ, Nore BF, Vihinen M, Smith CIE: Bruton’s tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling. Immunol Rev. 2005, 203: 200-215. 10.1111/j.0105-2896.2005.00225.x.CrossRefPubMed

15.

Gauld SB, Dal Porto JM, Cambier JC: B cell antigen receptor signaling: roles in cell development and disease. Science. 2002, 296: 1641-1642. 10.1126/science.1071546.CrossRefPubMed

16.

Lopez-Herrera G, Berron-Ruiz L, Mogica-Martinez D, Espinosa-Rosales F, Santos-Argumedo L: Characterization of Bruton’s tyrosine kinase mutations in Mexican patients with X-linked agammaglobulinemia. Mol Immunol. 2008, 45: 1094-1098. 10.1016/j.molimm.2007.07.022.CrossRefPubMed

17.

Kaveri SV, Maddur MS, Hegde P, Lacroix-Desmazes S, Bayry J: Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy. Clin Exp Immunol. 2011, 164 (Suppl 2): 2-5.CrossRefPubMedPubMedCentral

18.

Cho YK, Kook H, Woo YJ, Choi YY, Ma JS, Hwang TJ: Morganella morganii pericarditis in a child with X-linked agammaglobulinemia. Pediatr Int. 2010, 52: 489-491.CrossRefPubMed

19.

Kanegane H, Futatani T, Wang Y, Nomura K, Shinozaki K, Matsukura H, Kubota T, Tsukada S, Miyawaki T: Clinical and mutational characteristics of X-linked agammaglobulinemia and its carrier identified by flow cytometric assessment combined with genetic analysis. J Allergy Clin Immunol. 2001, 108: 1012-1020. 10.1067/mai.2001.120133.CrossRefPubMed

20.

Wang Y, Kanegane H, Sanal O, Ersoy F, Tezcan I, Futatani T, Tsukada S, Miyawaki T: Bruton tyrosine kinase gene mutations in Turkish patients with presumed X-linked agammaglobulinemia. Hum Mutat. 2001, 18: 356-356.CrossRefPubMed

21.

Hashimoto S, Tsukada S, Matsushita M, Miyawaki T, Niida Y, Yachie A, Kobayashi S, Iwata T, Hayakawa H, Matsuoka H, Tsuge I, Yamadori T, Kunikata T, Arai S, Yoshizaki K, Taniguchi N, Kishimoto T: Identification of Bruton’s tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families: a nationwide study of Btk deficiency in Japan. Blood. 1996, 88: 561-573.PubMed

22.

Aghamohammadi A, Cheraghi T, Rezaei N, Kanegane H, Abdollahzede S, Talaei-Khoei M, Heidari G, Zandieh F, Moin M, Miyawaki T: Neutropenia associated with X-linked agammaglobulinemia. Iranian J Allergy, Asthma Immunol. 2009, 8: 43-47.

23.

Plo Rodríguez F, García Rodríguez MC, Ferreira Cerdán A, Fontán Casariego G: Neutropenia as early manifestation of X-linked agammaglobulinemia. Report on 4 patients. An Esp Pediatr. 1999, 51: 235-240.PubMed

24.

Farrar JE, Rohrer J, Conley ME: Neutropenia in X-linked agammaglobulinemia. Clin Immunol Immunopathol. 1996, 81: 271-276. 10.1006/clin.1996.0188.CrossRefPubMed

25.

Kanegane H, Taneichi H, Nomura K, Futatani T, Miyawaki T: Severe neutropenia in Japanese patients with x-linked agammaglobulinemia. J Clin Immunol. 2005, 25: 491-495. 10.1007/s10875-005-5370-x.CrossRefPubMed

26.

Cham B, Bonilla MA, Winkelstein J: Neutropenia associated with primary immunodeficiency syndromes. Semin Hematol. 2002, 39: 107-112. 10.1053/shem.2002.31916.CrossRefPubMed

27.

Honda F, Kano H, Kanegane H, Nonoyama S, Kim E-S, Lee S-K, Takagi M, Mizutani S, Morio T: The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils. Nat Immunol. 2012, 13: 369-378. 10.1038/ni.2234.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/129/prepub

Title: Clinical and mutational features of Vietnamese children with X-linked agammaglobulinemia
Authors: Quang Van Vu
Taizo Wada
Huong Thi Minh Le
Hai Thanh Le
Anh Thi Van Nguyen
Ohara Osamu
Akihiro Yachie
Sang Ngoc Nguyen
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Pediatrics / Issue 1/2014
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/1471-2431-14-129

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Clinical and mutational features of Vietnamese children with X-linked agammaglobulinemia

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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