How rare is activated PI3K-delta syndrome?

activated PI3K-delta syndrome is classified as not well established. The estimated prevalence is approximately Unknown. Because rare disease data can be limited, actual numbers may differ from published estimates.

How is activated PI3K-delta syndrome diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for activated PI3K-delta syndrome?

Information about treatment is currently limited for this condition.

What complications can arise from activated PI3K-delta syndrome?

Information about complications related to activated PI3K-delta syndrome is currently limited. However, patients may experience issues with their immune system, which can lead to increased infections or other health problems. It's important to work closely with a healthcare provider to monitor any potential complications.

How does activated PI3K-delta syndrome affect daily life?

Daily life for someone with activated PI3K-delta syndrome can be challenging due to potential immune system issues. This may mean more frequent doctor visits and careful management of health to prevent infections. Families often need to adjust activities to ensure safety and health.

What is the life expectancy for someone with activated PI3K-delta syndrome?

Currently, there is limited information about the life expectancy of individuals with activated PI3K-delta syndrome. Since this condition can affect the immune system, it is essential for patients to receive proper care and monitoring. Regular check-ups with healthcare providers can help manage the condition effectively.

Are there any specific specialists recommended for activated PI3K-delta syndrome?

While specific recommendations for specialists are not detailed, patients with activated PI3K-delta syndrome may benefit from seeing immunologists or geneticists. These specialists can help manage the immune system issues and provide guidance on living with the condition. It's important to find healthcare providers who understand rare diseases.

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activated PI3K-delta syndrome (APDS) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

activated PI3K-delta syndrome

MONDO:0018338

Also known as:APDSsenescent T-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-activating mutation

Overview

OnsetCHILDHOOD

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: childhood.

GeneReviews

Clinical Guidance

Activated PI3K delta syndrome (APDS) is a rare inborn error of immunity characterized primarily by frequent infections, lymphoproliferation, and autoimmune manifestations. To date, at least 250 individuals have been identified with a pathogenic variant in PIK3CD (for APDS1) or PIK3R1 (for APDS2) [, , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. It is important to note that the severity and presence of these clinical findings can vary widely among affected individuals. Some may present with mild symptoms, while others experience severe manifestations that significantly impact quality of life. The variability within the spectrum of APDS highlights the importance of individualized care and management strategies. Table 2. Activated PI3K Delta Syndrome: Frequency of Select Features

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

No consensus clinical diagnostic criteria for activated PI3K delta syndrome (APDS) have been published.

Suggestive Findings

APDS types 1 (APDS1) and 2 (APDS2) are characterized by a spectrum of clinical manifestations primarily involving the immune system, leading to increased susceptibility to infections, autoimmunity, and lymphoproliferation. APDS should be considered in probands with the following suggestive findings:

Clinical findings

Source: GeneReviews —

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for activated PI3K-delta syndrome. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for activated PI3K delta syndrome (APDS) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with APDS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 8. Activated PI3K Delta Syndrome: Recommended Surveillance

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for activated PI3K-delta syndrome.

52 publications have been identified in PubMed for activated PI3K-delta syndrome. Research spans Case Report / Case Series (33%), Epidemiology / Natural History (17%), and Basic Science / Preclinical (13%).

Research Type	Count	% of Total
Patient case studies	17	33%

Data assembled from 4 of 12 sources · Last updated Sep 19, 2026, 1:06 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:397596

GARD

Genetic and Rare Diseases Info Center

GARD:11983

Questions for Your Care Team

→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

FAQ

Frequently Asked Questions

Common questions about activated PI3K-delta syndrome

Information about overview is currently limited for this condition.

Information about symptoms is currently limited for this condition.

Information about causes is currently limited for this condition. Associated genes include PIK3CD, PIK3R1.

← Back to All Diseases

Feature	% of Persons w/Feature	Comment
Sinopulmonary infections	96%-100%	Severe /or recurrent
Bronchiectasis	18%-60%	—
Lymphoproliferation	71%-89%	Incl splenomegaly, hepatomegaly, lymphadenopathy
Growth delays	45%-62%	—
Herpes virus infections	36%-49%	Persistent, severe, /or recurrent
Enteropathy	25%-51%	Lymphoid aggregates may be seen on histology.
Lymphoma	12%-28%	Particularly early onset
Autoimmune cytopenias	19%-30%	May be refractory to conventional therapy
Autoimmune autoinflammatory disease	17%-42% Neurodevelopmental delay	19%-31%

GeneReviews

Differential Diagnosis

Table 4. Genes of Interest in the Differential Diagnosis of Activated PI3K Delta Syndrome

Gene(s)	Disorder	MOI	Features of Disorder
AICDA	Hyper IgM syndrome 2 (HIGM2) (OMIM 605258)	AR	Recurrent infections, hypogammaglobulinemia, IgM, lymphoid hyperplasia
TNFRSF13C	Common variable immunodeficiency (CVID) (OMIM PS607594)	ARAD	Recurrent infections, hypogammaglobulinemia, autoimmunity, lymphoproliferation
CD40	Hyper IgM syndrome 3 (HIGM3) (OMIM 606843)	AR	Recurrent infections, hypogammaglobulinemia, IgM, lymphoid hyperplasia
CD40LG	X-linked hyper IgM syndrome (HIGM1)	XL SH2D1A XIAP	—
X-linked lymphoproliferative disease	XL	Immune dysregulation	More severe EBV infections
UNG	Hyper IgM syndrome 5 (HIGM5) (OMIM 608106)	AR	Recurrent infections
CTLA4	CTLA4 haploinsufficiency (OMIM 616100)	AD	Recurrent infections, autoimmunity, lymphoproliferation
LRBA	LRBA deficiency (OMIM 614700)	AR	—
STAT3	Autoimmune disease, multisystem, infantile-onset, 1 (OMIM 615952)	AD1	T helper 17 cells phosphorylated STAT3 AD = autosomal dominant; APDS = activated PI3K delta syndrome; AR = autosomal recessive; CTLA-4 = cytotoxic T-lymphocyte protein 4; EBV = Epstein-Barr virus; MOI = mode of inheritance; STAT3 = signal transducer and activator of transcription 3; XL = X-linked 1.

Source: GeneReviews — "Activated PI3K Delta Syndrome"

Kisho

activated PI3K-delta syndrome

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

Differential Diagnosis

General

Infection history

Immunodeficiency

Lymphoproliferation

Pulmonary

Gastrointestinal

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder Complicated by Septic Shock in Activated PI3Kδ Syndrome: A Pediatric Case Report and Literature Review.

A review of PI3K/AKT/mTOR inhibitors from traditional Chinese medicine: potential and perspective for activated phosphoinositide 3-kinase δ syndrome.

activated PI3K-delta syndrome

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

What is activated PI3K-delta syndrome?

What are the symptoms of activated PI3K-delta syndrome?

What causes activated PI3K-delta syndrome?

How rare is activated PI3K-delta syndrome?

How is activated PI3K-delta syndrome diagnosed?

Are there treatments for activated PI3K-delta syndrome?

What complications can arise from activated PI3K-delta syndrome?

How does activated PI3K-delta syndrome affect daily life?

What is the life expectancy for someone with activated PI3K-delta syndrome?

Are there any specific specialists recommended for activated PI3K-delta syndrome?

Differential Diagnosis

General

Infection history

Immunodeficiency

Lymphoproliferation

Pulmonary

Gastrointestinal

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder Complicated by Septic Shock in Activated PI3Kδ Syndrome: A Pediatric Case Report and Literature Review.

A review of PI3K/AKT/mTOR inhibitors from traditional Chinese medicine: potential and perspective for activated phosphoinositide 3-kinase δ syndrome.