SCIENTIFIC BACKGROUND

BTK

Category:

Scientific Background

X-linked agammaglobulinemia (XLA) (incidence approximately 1:100,000) is a primary humoral immunodeficiency syndrome based on a B cell maturation disturbance. The clinical symptoms begin between the 4th and 12th month of life with severe bacterial infections (such as otitis media, pneumonia, meningitis and sepsis) caused especially by encapsulated germs. One of the most common infections is chronic sinusitis. Although the defense against viral infections is generally not impaired, patients are susceptible to enterovirus infections. Some of those affected develop chronic infections such as dermatomyositis or meningoencephalitis, and about 20% develop arthritis.

 

The B cell maturation disturbance shows itself through massively reduced B cell counts and an almost complete absence of plasma cells and immunoglobulins of all isotypes. T lymphocyte numbers and functions are normal. Despite the frequent infections small or missing tonsils, adenoids and lymph nodes are noticed during clinical examination. The therapy consists of the administration of immunoglobulins and antibiotics according to the pathogen. Complications include chronic lung disease and an increased risk of colon cancer and lymphoreticular malignancies.

 

XLA is caused by pathogenic variants in the BTK gene, which is located on the X chromosome. Pathogenic variants in the BTK gene are identifiable in about 90% of patients with suspected XLA. Pathogenic variants in other genes essential for normal B cell maturation are detectable in the majority of cases in males without detectable variants in the BTK gene and in female patients with an XLA-like phenotype (see hereditary agammaglobulinemia,). Obligate female carriers show a "non-random" X inactivation in their B cells.

 

References

Smith et al. 2016, GeneReviews® [Internet], https://www.ncbi.nlm.nih.gov/books/NBK1453/ / El-Sayed et al. 2019, World Allergy Organ J 12:100018 / Chen et al. 2016, Medicine (Baltimore) 95:e4544 / Lee et al. 2010, J Clin Immunol 30:121 / XLA in: Stiehm, Ochs, Winkelstein: Immunologic conditions in infants and children 5th Edition

GENES

BTK

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Overview In January 2024, the American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology (SSO) published new recommendation...

Read more

Endometriosis is a chronic gynecological condition that affects 1 in 10 women of reproductive age worldwide [1]. It can manifest with the first menst...

Read more

Rare Disease Day is a global awareness day held annually to raise awareness of all rare diseases. It was first celebrated in 2008, on the rarest day ...

Read more

Cancer is a group of genetic diseases that can develop almost anywhere in the body. Many people in the world are affected by cancer every year. Follo...

Read more

Aiming to evaluate the role of chromosomal aneuploidy in pregnancy loss, a 2023 study 35 years in the making evaluated the genomic landscape of first...

Read more

Cancer is a complex genetic disease that affects millions of people in the world. It is one of the leading causes of death worldwide, with about ten ...

Read more

Researchers created a detailed map of the placenta during labor. By studying how maternal and fetal cells communicate, they discovered signals in the...

Read more

A recent paper published in Nature Medicine (1) aimed to identify genes and genomic biomarkers which can better predict outcomes and personalized the...

Read more

In honor of the international day of women and girls in science, we interviewed one of our very own, Dr. Evelina Papaioannou. Dr. Evelina Pa...

Read more

Aneuploidies, such as translocations, whole or segmental chromosomal duplications, and deletions, are examples of chromosomal abnormalities that are ...

Read more