Activated PI3K Delta Syndrome (APDS) is an underdiagnosed, 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 Signs & Symptoms
Learn more about APDS at allaboutapds-hcp.com.
Reevaluating Diagnosis
Since APDS shares many features of other immune disorders, patients with APDS may have a previous diagnosis. 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
Informing the Diagnosis
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
Help 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 help inform an APDS diagnosis.
That’s why Pharming Healthcare, Inc. has partnered with Invitae (now part of Labcorp) to offer sponsored 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.
Sponsored Program Eligibility
navigateAPDS (the “Program”) is a genetic testing program sponsored by Pharming Healthcare, Inc. (“Pharming”). All testing is performed by Invitae (a part of Labcorp). The Program is available to patients in the US, Canada, and US Territories who meet the clinical eligibility criteria set forth below, as confirmed by a Healthcare professional.
The purpose of the Program is to help eligible patients and physicians make better informed decisions about the patient’s appropriate course of treatment. Sponsored genetic testing and genetic counseling are available for eligible patients regardless of insurance coverage or financial need. Patients are not required to provide documentation that they are uninsured or that their insurance has denied coverage of the test. Patients do not need to meet financial need criteria, such as having an income below a certain amount. Healthcare professionals and patients who participate in the Program have no obligation to recommend, purchase, order, prescribe, promote, administer, use or support any products or services from Pharming or any other third party or commercial organization.
Testing Performed
APDS occurs when there is a disease-causing variant in either one of two specific genes, the PIK3CD gene or the PIK3R1 gene, in an autosomal dominant mode of inheritance. Healthcare professionals ordering tests for eligible patients under the Program may select (a) one of two genetic testing panels or (b) a PIK3CD or PIK3R1 single gene test, both offered by Invitae to identify genetic variants associated with a broad range of inherited disorders of the immune system. Panels include testing for gene variants in PIK3CD or PIK3R1 that may indicate APDS, in addition to other gene variants that potentially indicate other inherited disorders. A single gene test for PIK3CD or PIK3R1 is typically used when there is a known family variant in either of those genes. A positive test for either one of the two genes (PIK3CD or PIK3R1) may result in a definitive molecular diagnosis of APDS.
The Invitae Primary Immunodeficiency Panel analyzes genes that are associated with inherited disorders of the immune system. These genes were selected based on the available evidence to date and comprise Invitae’s broadest test for primary immunodeficiencies (PIDs).
The Invitae Inborn Errors of Immunity and Cytopenias Panel analyzes genes that are associated with inherited disorders of the immune system including inherited causes of cytopenia such as bone marrow failure, adult-onset cancer predisposition genes and hereditary lymphoma. These genes were selected based on the available evidence to date and comprise Invitae’s broadest test for inborn errors of immunity.
All testing is performed by Invitae.
Information Sharing and Outreach
Invitae will send the results of a test performed under the Program to the ordering healthcare professional. Pharming, as the sponsor of the Program, pays Invitae for and receives information about the number of tests performed under the Program. For patients who are covered under commercial insurance or who do not have insurance, Pharming also receives additional information for each test performed. Information provided to Pharming includes an anonymized patient identification number, the criteria that the patient met in order to be eligible for sponsored testing, certain patient demographic information such as age and sex, patient clinical history (including any family history of disease) provided on the test requisition form, information about the healthcare professional who ordered the test such as their name and contact information, and variants identified on the panel along with their classification. Information provided does not include the patient’s name, date of birth, or contact information.
If a patient tests positive for a disease-causing variants in PIK3CD or PIK3R1 that may indicate APDS, Pharming may use the test-specific information received about anonymous uninsured patients and patients with commercial insurance to reach out to the ordering healthcare professional. The outreach may seek to provide the healthcare professional with additional information about APDS and a potential treatment option.
Some insurers may require that a patient test positive for one of the disease-causing variants (PIK3CD or PIK3R1) that indicate APDS before the insurer will approve coverage for targeted APDS treatment. Test results are not shared directly with insurers. However, the patient or their provider may choose to share test results with their insurer.
The requisition form for ordering tests under the Program requires that the ordering healthcare professional indicate whether the patient is currently covered under a governmental insurance program. Pharming does not receive ordering provider information for participating patients covered under US governmental insurance programs such as Medicare and Medicaid. Completion of the questionnaire allows Invitae to identify those patients to ensure the ordering provider information is not shared with Pharming. This does not affect patient eligibility. Patients covered under a governmental insurance program may still be eligible to receive testing and the results of that testing at no charge.
Clinical Features
- Bronchiectasis
- Lymphadenopathy/lymphoproliferation
- Chronic hepatomegaly or chronic splenomegaly
- Severe, persistent, or recurrent Herpesviridae infection (e.g. EBV, CMV, VZV, HSV)
- Recurrent sinopulmonary infections
- Recurrent pneumonia
- Recurrent otitis media
- Nodular mucosal lymphoid hyperplasia
- Autoimmune or inflammatory organ involvement consistent with immune dysregulation (e.g., autoimmune forms of hepatitis, thyroiditis, nephritis, etc)
- Autoimmune cytopenia(s)
- Enteropathy (e.g. chronic/recurrent diarrhea, inflammatory bowel disease)
- Lymphoma (0-25 years) meets 3 eligibility criteria
- Lymphoma ≥26 years of age, requires 2 additional eligibility criteria
- Non-food related eosinophilic esophagitis
- Developmental delay
- Short stature or history of failure to thrive
- Hypogammaglobulinemia
Laboratory
- Elevated levels of Immunoglobulin M (IgM)
- Increased number of follicular helper T cells
- Reduced number of naive B cells
- Increased transitional B cells
- Inverted CD4/CD8 ratio (low CD4+ T helper cells and high senescent effector/memory CD8+ cells)
- Hyperactive PI3Kδ activity as assessed by phosphorylated AKT and/or phosphorylated S6
History
- Clinical diagnosis of Activated PI3K-Delta Syndrome (APDS) meets 3 eligibility criteria
- Common Variable Immune Deficiency (CVID) phenotype
- Family history of CVID
- Family member with PIK3CD or PIK3R1 pathogenic, likely pathogenic, or VUS result meets 3 eligibility criteria
If you suspect APDS, testing is the next step. Click below to see if your patient qualifies and order a test.
Request free Specimen Collection Kits:
Individual or multiple kits can be ordered through the link below.
Blood kits (EDTA)
Buccal swab kits
Saliva kits
Sponsored Genetic Counseling Is Available
After Testing
Individuals tested through the navigateAPDS program are eligible for post-test genetic counseling to help them understand their test results. This service is provided through Genome Medical, an independent genetic counseling service, and is made available by Pharming Healthcare, Inc.
If requested, patients will be contacted by Genome Medical to schedule an appointment.
Visit the Genome Medical website to Learn More.
Book Genetic Counseling
Post-test genetic counseling is available as part of the navigateAPDS program.
To refer a patient for genetic counseling, physicians can check the box* under the section titled Genetic Counseling while completing the Test Requisition Form (TRF).
TRFs can be completed through
Invitae’s online portal (preferred) or the paper form.
*Checking this box will authorize the laboratory to share the necessary information with Genome Medical to complete the post-test genetic counseling.
Need Assistance Understanding a Variant in PIK3CD/R1?
Genetic testing through navigateAPDS including access to board certified genetic counselors before, during, and after testing to help clinicians understand the testing options, process, and results.
Learn more about APDS at
References:
1. Activated PI3K-delta syndrome. Orphanet. Accessed April 26, 2021. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397596 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.
Pharming Healthcare, Inc. provides financial support for the genetic testing program and provides information about the program to healthcare professionals and others. Tests and services, however, are performed by Invitae. Healthcare professionals must confirm that patients meet certain criteria to use the program. Pharming Healthcare, Inc. and other third parties, including commercial organizations, may receive information about patients, the healthcare professionals ordering tests, and the test results, but at no time is any patient-identifiable information provided to Pharming Healthcare, Inc. Also, for tests involving patients covered under governmental health insurance programs such as Medicare and Medicaid, no information regarding the healthcare professional ordering the test is provided to Pharming Healthcare, Inc. Genetic testing and counseling are available in the US, Canada, and US Territories only. Healthcare professionals and patients who participate in the genetic testing program have no obligation to recommend, purchase, order, prescribe, promote, administer, use, or support any other products or services from the laboratory or from third parties or commercial organizations. Patients who participate in the genetic testing program are free to use the information received through the program to inform their physician and their own healthcare decision-making in any way they deem appropriate.
