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Activated PI3K-delta syndrome
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Reviewed July 2014
What is activated PI3K-delta syndrome?
Activated PI3K-delta syndrome is a disorder that impairs the immune system. Individuals with this condition often have low numbers of white blood cells (lymphopenia), particularly B cells and T cells. Normally, these cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. Beginning in childhood, people with activated PI3K-delta syndrome develop recurrent infections, particularly in the lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. People with activated PI3K-delta syndrome may also have chronic active viral infections, commonly Epstein-Barr virus or cytomegalovirus infections.
Another possible feature of activated PI3K-delta syndrome is abnormal clumping of white blood cells. These clumps can lead to enlarged lymph nodes (lymphadenopathy), or the white blood cells can build up to form solid masses (nodular lymphoid hyperplasia), usually in the moist lining of the airways or intestines. While lymphadenopathy and nodular lymphoid hyperplasia are noncancerous (benign), activated PI3K-delta syndrome also increases the risk of developing a form of cancer called B-cell lymphoma.
How common is activated PI3K-delta syndrome?
The prevalence of activated PI3K-delta syndrome is unknown.
What genes are related to activated PI3K-delta syndrome?
Activated PI3K-delta syndrome is caused by mutations in the PIK3CD gene, which provides instructions for making a protein called p110 delta (p110δ). This protein is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K), which turns on signaling pathways within cells. The version of PI3K containing the p110δ subunit, called PI3K-delta, is specifically found in white blood cells, including B cells and T cells. PI3K-delta signaling is involved in the growth and division (proliferation) of white blood cells, and it helps direct B cells and T cells to mature (differentiate) into different types, each of which has a distinct function in the immune system.
PIK3CD gene mutations involved in activated PI3K-delta syndrome lead to production of an altered p110δ protein. A PI3K-delta enzyme containing the altered subunit is abnormally turned on (activated). Studies indicate that overactive PI3K-delta signaling alters the differentiation of B cells and T cells, leading to production of cells that cannot respond to infections and that die earlier than usual. Lack of functioning B cells and T cells makes it difficult for people with this disorder to fight off bacterial and viral infections. Overactivation of PI3K-delta signaling can also stimulate abnormal proliferation of white blood cells, leading to lymphadenopathy and nodular lymphoid hyperplasia in some affected individuals. An increase in B cell proliferation in combination with reduced immune system function may contribute to development of B-cell lymphoma.
Read more about the PIK3CD gene.
How do people inherit activated PI3K-delta syndrome?
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
Where can I find information about diagnosis or management of activated PI3K-delta syndrome?
These resources address the diagnosis or management of activated PI3K-delta syndrome and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about activated PI3K-delta syndrome?
You may find the following resources about activated PI3K-delta syndrome helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for activated PI3K-delta syndrome?
What if I still have specific questions about activated PI3K-delta syndrome?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding activated PI3K-delta syndrome?
autosomal ; autosomal dominant ; bacteria ; benign ; bronchi ; bronchiectasis ; cancer ; cell ; cell proliferation ; chronic ; differentiation ; enzyme ; gene ; hyperplasia ; immune system ; immunodeficiency ; infection ; inherited ; kinase ; lymph ; lymphocyte ; lymphoid ; lymphoma ; lymphopenia ; mutation ; prevalence ; proliferation ; protein ; respiratory ; subunit ; syndrome ; virus ; white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (5 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.