Delayed diagnosis in X-linked agammaglobulinemia and its relationship to the occurrence of mutations in BTK non-kinase domains

Eduardo Carrillo-Tapia, Elizabeth García-García, Norma Estela Herrera-González, Marco Antonio Yamazaki-Nakashimada, Aidee Tamara Staines-Boone, Nora Hilda Segura-Mendez, Selma Cecilia Scheffler-Mendoza, Patricia O‘Farrill-Romanillos, Maria E. Gonzalez-Serrano, Juan Carloa Rodriguez-Alba, Leopoldo Santos-Argumedo, Laura Berron-Ruiz, Alejandro Sanchez-Flores, Gabriela López-Herrera

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: X-linked agammaglobulinemia (XLA) is characterized by the absence of immunoglobulin and B cells. Patients suffer from recurrent bacterial infections from early childhood, and require lifelong immunoglobulin replacement therapy. Mutations in BTK (Bruton’s Tyrosine Kinase) are associated with this phenotype. Some patients that present XLA do not show typical clinical symptoms, resulting in delayed diagnosis due to the lack of a severe phenotype. This study presents a report of five XLA patients from four different families and attempts to determine a relationship between delayed diagnosis and the occurrence of BTK mutations. Methods: Samples from patients with antibody deficiency were analyzed to determine BTK expression, immunophenotyping and mutation analysis. Clinical and laboratory data was analyzed and presented for each patient. Results: Most patients presented here showed atypical clinical and laboratory data for XLA, including normal IgM, IgG, or IgA levels. Most patients expressed detectable BTK protein. Sequencing of BTK showed that these patients harbored missense mutations in the pleckstrin homology and Src-homology-2 domains. When it was compared to public databases, BTK sequencing exhibited a new change, along with three other previously reported changes. Conclusions: Delayed diagnosis and atypical manifestations in XLA might be related to mutation type and BTK expression.

Original languageEnglish
Pages (from-to)83-93
Number of pages11
JournalExpert Review of Clinical Immunology
Volume14
Issue number1
DOIs
StatePublished - 2 Jan 2018

Keywords

  • Bruton tyrosine kinase (BTK)
  • Delayed X-linked agammaglobulinemia (XLA)
  • PH and SH2 domains
  • atypical phenotype

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