Overview
Activated PI3K-delta syndrome (also called APDS, or sometimes PASLI disease) is a rare genetic disorder of the immune system. It is caused by mutations in genes that control a signaling protein called PI3K-delta, which plays a key role in how immune cells develop and function. When this protein is overactive, it disrupts the normal workings of the immune system, leading to a primary immunodeficiency. People with APDS typically experience frequent and severe infections, especially of the lungs, ears, and sinuses, often starting in early childhood. The condition can also cause the lymph nodes, spleen, and other lymphoid tissues to become enlarged (called lymphoproliferation). Over time, repeated lung infections can lead to permanent lung damage known as bronchiectasis. Some patients develop autoimmune problems, where the immune system mistakenly attacks the body's own cells, and there is also an increased risk of developing lymphoma, a type of blood cancer. There are two subtypes: APDS1, caused by mutations in the PIK3CD gene, and APDS2, caused by mutations in the PIK3R1 gene. Treatment has traditionally focused on managing infections with antibiotics and supporting the immune system with immunoglobulin replacement therapy. More recently, targeted therapies that directly inhibit the overactive PI3K-delta pathway have become available, including the FDA-approved drug leniolisib (Joenja), which represents a significant advance for patients with this condition. Hematopoietic stem cell transplant may also be considered in severe cases.
Also known as:
Key symptoms:
Frequent sinus infectionsFrequent ear infectionsRecurrent pneumonia or lung infectionsEnlarged lymph nodesEnlarged spleenPermanent lung damage (bronchiectasis)Frequent herpes virus infections (such as EBV or CMV)Low levels of antibodies in the bloodAutoimmune problems like low blood cell countsGrowth delay or short statureChronic diarrhea or digestive problemsIncreased risk of lymphoma (a type of blood cancer)Fatigue and low energyWarts or other viral skin infections
Clinical phenotype terms (24)— hover any for plain English
Autosomal dominant
Passed on from just one parent; each child has about a 50% chance of inheriting it
Childhood
Begins in childhood, roughly ages 1 to 12
FDA & Trial Timeline
7 eventsAssistance Publique - Hôpitaux de Paris
Pharming Technologies B.V. — PHASE3
Joenja: FDA approved
treatment of activated phosphoinositide 3-kinase delta (PI3K delta) syndrome (APDS) in adult and pediatric patients 12 years of age and older
Pharming Technologies B.V. — PHASE3
Magentiq Eye LTD
General and Teaching Hospital Celje — PHASE1
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
1 availableJoenja
treatment of activated phosphoinositide 3-kinase delta (PI3K delta) syndrome (APDS) in adult and pediatric patients 12 years of age and older
Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Financial Resources
1 resourcesTravel Grants
No travel grants are currently matched to Activated PI3K-delta syndrome.
Community
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Start the conversation →Latest news about Activated PI3K-delta syndrome
Disease timeline:
New recruiting trial: Collecting Recorded Videos of Colonoscopy and Gastroscopy Tests for the Evaluation of the (ME-APDS).
A new clinical trial is recruiting patients for Activated PI3K-delta syndrome
New recruiting trial: Collecting Recorded Videos of Colonoscopy
A new clinical trial is recruiting patients for Activated PI3K-delta syndrome
New recruiting trial: New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase δ Syndrome
A new clinical trial is recruiting patients for Activated PI3K-delta syndrome
Caregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
Rare disease caregiving can be isolating. Connect with counseling and peer support.
Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Questions for your doctor
Bring these to your next appointment
- Q1.Which subtype of APDS does my child (or I) have, and what does that mean for treatment?,Is leniolisib (Joenja) appropriate for my case, and how do I access it?,How often will immunoglobulin replacement therapy be needed, and can it be done at home?,What signs of lymphoma should I watch for, and how often should screening be done?,Should my family members be tested for the same genetic mutation?,Is stem cell transplant something we should consider now or in the future?,What vaccines are safe, and which ones should be avoided?
Common questions about Activated PI3K-delta syndrome
What is Activated PI3K-delta syndrome?
Activated PI3K-delta syndrome (also called APDS, or sometimes PASLI disease) is a rare genetic disorder of the immune system. It is caused by mutations in genes that control a signaling protein called PI3K-delta, which plays a key role in how immune cells develop and function. When this protein is overactive, it disrupts the normal workings of the immune system, leading to a primary immunodeficiency. People with APDS typically experience frequent and severe infections, especially of the lungs, ears, and sinuses, often starting in early childhood. The condition can also cause the lymph nodes,
How is Activated PI3K-delta syndrome inherited?
Activated PI3K-delta syndrome follows a autosomal dominant inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does Activated PI3K-delta syndrome typically begin?
Typical onset of Activated PI3K-delta syndrome is childhood. Age of onset can vary across affected individuals.
Are there clinical trials for Activated PI3K-delta syndrome?
Yes — 4 recruiting clinical trials are currently listed for Activated PI3K-delta syndrome on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.
Which specialists treat Activated PI3K-delta syndrome?
15 specialists and care centers treating Activated PI3K-delta syndrome are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.
What treatment and support options exist for Activated PI3K-delta syndrome?
1 patient support program are currently tracked on UniteRare for Activated PI3K-delta syndrome. See the treatments and support programs sections for copay assistance, eligibility, and contact details.