For U.S Healthcare Professionals

For Healthcare Professionals

For Healthcare Professionals

Activated PI3K Delta Syndrome (APDS) is a rare, genetic primary immunodeficiency

If you suspect your patient may have APDS, it’s time to test.

Activated PI3K Delta Syndrome (APDS) is a rare, genetic primary immunodeficiency

If you suspect your patient may have APDS, it’s time to test.

Learn About APDS

APDS is a rare primary immunodeficiency (also known as an inborn error of immunity – IEI), which affects approximately 1-2 people per million. It occurs when there is an autosomal dominant variant in either of two genes, PIK3CD or PIK3R1, which make parts of the PI3K delta protein that helps control the development and function of B and T cells. 1-4

APDS Signs & Symptoms

Signs and symptoms of APDS can start in childhood, and patients are vulnerable to repeat infections and immune dysregulation such as lymphadenopathy, splenomegaly, autoimmune cytopenias, and even lymphoma. 9

Learn more about APDS at

Avoid Misdiagnosis

Since APDS shares many features of other immune disorders, patients with APDS may have been previously misdiagnosed with other conditions. 5 APDS may be mistaken for common variable immune deficiency (CVID) or hyper IgM syndrome (HIGM), while hematologists may not realize their patient with refractory cytopenias or autoimmune lymphoproliferative syndrome (ALPS) actually has APDS. 5-7

Get a Definitive Diagnosis

Genetic testing can definitively diagnose APDS and other primary immunodeficiencies, which may have targeted treatment options and help identify patients for participation in clinical research. 6-8
A suboptimal response to treatment should raise suspicion of an IEI, like APDS11
Timeline of the most common pathologies seen in APDS 5,9,10*

*Onset of all symptoms is heterogenous and typically progressive, varying from patient to patient

Definitively Diagnose APDS With Genetic Testing

The heterogenous signs and symptoms of APDS can often be attributed to other conditions, only leading to more questions. Once suspected, genetic testing can confirm the APDS diagnosis.

That’s why Pharming Healthcare, Inc. has partnered with Invitae to offer no-charge genetic testing and counseling for individuals who are suspected to have APDS.

Early, accurate diagnosis can change a person’s life and help get timely appropriate treatments.

Dr. Nicholas Hartog


No-Charge Program Eligibility

NavigateAPDS is a sponsored, no-charge genetic testing program available to individuals in the U.S. and Canada who meet any two of the bulleted criteria below:

Clinical Features

  • Onset of symptoms under 12 years of age
  • Documented severe recurrent sinopulmonary infections (>2 events within 3 years of each other)
  • Bronchiectasis
  • Lymphadenopathy for greater than one month
  • Any nodular lymphoid hyperplasia
  • Chronic hepatomegaly or chronic splenomegaly
  • Severe, persistent, or recurrent Herpesviridae infections (eg, EBV, cytomegalovirus)
  • Autoimmune cytopenia
  • Enteropathy
  • Lymphoma at 0-25 years – meets the 2 eligibility criteria
  • Lymphoma at ≥26 years of age – requires second eligibility criteria


  • Hypogammaglobulinemia
  • Elevated levels of immunoglobulin M
  • Reduced number of CD3+CD4+ T cells;
  • Increased number of follicular helper T cells
  • Reduced number of naïve T cells


  • Primary Immune Deficiency diagnosis
  • Common Variable Immune Deficiency (CVID) phenotype or direct family member with CVID phenotype
  • Relative with PIK3CD or PIK3R1 genotype (first or second degree)
If you suspect APDS, and your patient meets the program criteria, testing is the next step.

Ordering Multiple Tests for Family Members?
Get Free Test Kits:

Blood Kit
+ EDTA (purple-top) blood tube
Buccal Swab Kit
+ Two (2) – ORAcollect Dx
(OCD-100) Buccal Swabs
Saliva Kit
+ Saliva (OG-500/510)
collection tube

No-Charge Genetic Counseling Is Available
Both Before and After Testing

Individuals tested through the navigateAPDS program are eligible for both pre-test and post-test genetic counseling to help them understand their test results. This service is provided through GeneMatters, an independent genetic counseling service and is made available by Pharming at no charge. If requested, patients will be contacted by GeneMatters to schedule an appointment.

Visit the GeneMatters website to Learn More

Book Genetic Counseling

There are two ways to access genetic counseling as part of the navigateAPDS program.

Option 1

Physicians can ‘check’ the box on the Invitae Test Requisition Form on the bottom of page 1, authorizing Invitae to share the necessary information with GeneMatters to complete the post-genetic counseling.

Option 2

Complete and fax the separate referral form provided below, requesting pre- and/or post-test genetic counseling.

Learn more about APDS at

1. Activated PI3K-delta syndrome. Orphanet. Accessed April 26, 2021. 2. Lucas CL, et al. Nat Immunol. 2014;15:88-97. 3. Angulo I, et al. Science. 2013;342(6160):866-871. 4. Lucas CL, et al. J Exp Med. 2014;211(13):2537-2547. 5. Jamee M, et al. Clin Rev Allergy Immunol. 2020;59(3):323-333 6. Rotz, SJ, et al. Pediatr Blood Cancer. 2018; 65:e27260. 7. Kulm E, et al. Oral abstract presented at the 62nd Annual ASH Meeting; Dec 5-8, 2020 8. Chinn IK, et al. J Allergy Clin Immunol. 2020;145(1):46-69. 9. Maccari ME et al. Front. Immunol. 2018;9:543 10. Elkaim E et al. J Allergy Clin Immunol. 2016;138(1):210-218. 11. Castagnoli R, et al. World Allergy Organ J. 2021;14(2):100513.

While third parties and commercial organizations may provide financial support for this program, tests and services are performed by Invitae. Healthcare professionals must confirm that patients meet certain criteria to use the program. Third parties and commercial organizations may receive de-identified patient data from this program, but at no time would they receive patient identifiable information. Third parties and commercial organizations may receive contact information for healthcare professionals who use this program. Genetic testing and counseling are available in the US and Canada only. Healthcare professionals and patients who participate in this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use or support any other products or services from Invitae or from third parties or commercial organizations.