Activated PI3K delta syndrome (APDS) is a form of primary immunodeficiency (PI). There are fewer than 100 reported cases of the condition. APDS has two types (1 and 2), depending on which gene mutation caused it. But since they are so similar in presentation to each other and many other types of PI’s, it’s hard to get the correct diagnosis. Many patients are first misdiagnosed. Thankfully, improved genetic testing has lessened this problem for patients. APDS 1 is caused by a mutation in the PI3KCD gene whereas APDS 2 is the result of a mutation in the PI3KR1 gene.
To help researchers better understand the presentations of APDS 1 and 2, a study was recently conducted evaluating their differences in two patients.
The first patient was a 13 year old diagnosed with APDS 1. He began to show symptoms while he was still an instant. He had recurrent infections, suffered from hepatosplenomegaly, lymphoproliferation, early portal hypertension, as well as hypogammaglobulinemia. However, his diagnosis did not come until he was a few years old as there wasn’t any access to genetic testing.
Researchers found he did have a PI3KCD gene mutation. He was able to successfully undergo a hematopoietic stem cell transplant which relieved him of the majority of his symptoms.
The second patient was an 11 year old diagnosed with APDS 2. For him, symptoms also presented in early childhood. Unfortunately, he wasn’t diagnosed with an immunodeficiency until he was 10. Thankfully, once the suspicion of his diagnosis was strong enough to make the decision to undergo testing, it took just a few months to get the results. This was due to the widespread availability of Next-Generation Sequencing (NGS) in Poland. He was found to have a PI3KR1 gene mutation.
This boy had facial dysmorphism, respiratory infections, and growth retardation since he was a young child. He also had panhypoglobulinemia, an impaired response to vaccines, and systemic lymphoproliferation (which was unfortunately worsened due to the use of growth hormones).
Ultimately, these researchers have shown that those who are suspected to have APDS or Common Variable Immunodeficiency (CVID) but who have other symptoms should undergo NGS genetic testing. These symptoms include-
- Facial dysmorphia
- Intellectual disability
- Short stature
- No response to human immunoglobulin replacement therapy
- Enhanced lymphoproliferation
However, because limitations to this type of testing still exist, researchers are still aiming to better define clinical presentations and biomarkers of APDS1 and 2.
Better understanding of these conditions will lead to earlier diagnosis, the establishment of a standard of care for their unique presentation, and better outcomes for patients.