APDS is inherited in an autosomal dominant manner, meaning that a person needs a pathalogical variant from only one parent to have it themselves. 1-4
De novo variants have also been observed, and while the prevalence has not been fully assessed, a large cohort suggests that around 20% of APDS patients may have de novo variants. 1-5
However, APDS may be difficult to trace based on clinical history as symptoms can vary even within the same family. 1
According to Nicholas Hartog, MD “Patients may have multiple complications though lack of a unified diagnosis.”
Some individuals may be misdiagnoised with other primary immunodeficiencies such as Common Variable Immune Deficiency (CVID) or Hyper IgM Syndromes.
Individuals whose main symptoms are autoimmune cytopenias, lymphandenopathy, splenomegaly, hepatomegaly, nodular lymphoid hyperplasia or lymphoma may be misdiagnosed with hematological disorders such as Autoimmune Lymphoproliferative Syndrome (ALPS), Evans syndrome, or simply refractory cytopenias.
Pharming Healthcare, Inc. a pharmaceutical company, has partnered with the genetic testing company Invitae to offer, at no-charge, genetic testing and counseling for individuals who may carry a pathogenic variant in one of two genes known to be associated with Activated PI3K Delta Syndrome (APDS), a rare primary immunodeficiency.
The navigateAPDS testing program helps eliminate barriers to genetic testing and increases certainty in obtaining a correct diagnosis by enabling patients suspected of having APDS, and their family members, to have access to genetic testing and counseling.
As there is a 50% chance of APDS being passed from parent to child, family members of patients with APDS should also be genetically tested.
PI is also referred to as an Inborn Error of Immunity (IEI).
1. Lucas CL, Kuehn HS, Zhao F, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15(1):88-97. doi:10.1038/ni.2771 2. AAngulo I, Vadas O, Garçon F, et al. Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage. Science. 2013;342(6160):866-871. doi:10.1126/science.1243292 3. Lucas CL, Zhang Y, Venida A, et al. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. J Exp Med. 2014;211(13):2537-2547. doi:10.1084/jem.20141759 4. Deau MC, Heurtier L, Frange P, et al. A human immunodeficiency caused by mutations in the PIK3R1 gene [published correction appears in J Clin Invest. 2015 Apr;125(4):1764-5]. J Clin Invest. 2014;124(9):3923-3928. doi:10.1172/JCI75746 5. Elkaim E, Neven B, Bruneau J, et al. Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study. J Allergy Clin Immunol. 2016;138(1):210-218.e9. doi:10.1016/j.jaci.2016.03.022 6. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.e4. 7. Walter JE, et al. J Allergy Clin Immunol Pract. 2016;4(6):1089-1100. 8. Kubala SA, et al. Poster presented at: CIS 2021 Annual Meeting; April 14-17, 2021 9. Jamee M, et al. Clin Rev Allergy Immunol. 2020;59(3):323-333. 10. Maccari ME, et al. Front Immunol. 2018;9:543. 11. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218. 12. Carpier JM, Lucas CL.Front Immunol. 2018;8:200 13. Castagnoli R, et al. World Allergy Organ J. 2021;14(2):100513 14. Angulo I, et al. Science. 2013;342(6160):866-871 15. Lucas CL, et al. Nat Immunol. 2014;15(1):88-97. 16. Condliffe AM, Chandra A. Front Immunol. 2018;9:338.
