X-linked lymphoproliferative disease due to SAP deficiency

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ORPHA:538931OMIM:308240D82.3
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Overview

X-linked lymphoproliferative disease due to SAP deficiency, also known as XLP1 or Duncan disease, is a rare inherited immune system disorder that affects almost exclusively males. It is caused by changes (mutations) in the SH2D1A gene, which provides instructions for making a protein called SAP (SLAM-associated protein). SAP plays a critical role in helping immune cells — especially T cells and NK cells — work properly and communicate with each other. In XLP1, the immune system fails to control a common virus called Epstein-Barr virus (EBV), also known as the virus that causes mono (mononucleosis). When boys with XLP1 are exposed to EBV, their immune system can go into dangerous overdrive, leading to a life-threatening condition called hemophagocytic lymphohistiocytosis (HLH), where immune cells start attacking the body's own tissues and organs. Even without EBV infection, affected individuals are at high risk for developing low antibody levels (hypogammaglobulinemia) and certain blood cancers called lymphomas. The main treatments include immunoglobulin replacement therapy to boost antibody levels, chemotherapy and steroids to control HLH episodes, and hematopoietic stem cell transplantation (bone marrow transplant), which is currently the only potentially curative treatment. Early diagnosis and transplant before EBV exposure offer the best outcomes.

Also known as:

Key symptoms:

Severe or life-threatening reaction to Epstein-Barr virus (EBV) infectionProlonged high fever that does not go awayEnlarged spleen and liverSwollen lymph nodesLow blood counts (anemia, low platelets, low white blood cells)Frequent or unusual infections due to low antibody levelsAbnormal immune cell activity attacking the body's own organs (HLH)Lymphoma (a type of blood cancer)Jaundice (yellowing of skin and eyes)Extreme fatigue and weaknessEasy bruising or bleedingNeurological symptoms such as confusion or seizures during HLH episodes

Inheritance

X-linked recessive

Carried on the X chromosome; typically affects males more than females

Age of Onset

Childhood

Begins in childhood, roughly ages 1 to 12

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for X-linked lymphoproliferative disease due to SAP deficiency.

View clinical trials →

No actively recruiting trials found for X-linked lymphoproliferative disease due to SAP deficiency at this time.

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Search ClinicalTrials.gov ↗Join the X-linked lymphoproliferative disease due to SAP deficiency community →

No specialists are currently listed for X-linked lymphoproliferative disease due to SAP deficiency.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to X-linked lymphoproliferative disease due to SAP deficiency.

Search all travel grants →NORD Financial Assistance ↗

Community

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Caregiver Resources

NORD Caregiver Resources

Support, advocacy, and financial assistance for caregivers of rare disease patients.

Mental Health Support

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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.Should my son have a bone marrow transplant, and how soon should we plan for it?,How do we find out if other male relatives in our family might also have XLP1?,What steps should we take to protect my son from EBV infection before transplant?,What are the signs of HLH, and what should I do if I think it is happening?,Does my son need regular IVIG infusions, and how will we manage those?,Are there any clinical trials or new treatments we should consider?,What long-term monitoring will my son need after a bone marrow transplant?

Common questions about X-linked lymphoproliferative disease due to SAP deficiency

What is X-linked lymphoproliferative disease due to SAP deficiency?

X-linked lymphoproliferative disease due to SAP deficiency, also known as XLP1 or Duncan disease, is a rare inherited immune system disorder that affects almost exclusively males. It is caused by changes (mutations) in the SH2D1A gene, which provides instructions for making a protein called SAP (SLAM-associated protein). SAP plays a critical role in helping immune cells — especially T cells and NK cells — work properly and communicate with each other. In XLP1, the immune system fails to control a common virus called Epstein-Barr virus (EBV), also known as the virus that causes mono (mononucle

How is X-linked lymphoproliferative disease due to SAP deficiency inherited?

X-linked lymphoproliferative disease due to SAP deficiency follows a x-linked recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does X-linked lymphoproliferative disease due to SAP deficiency typically begin?

Typical onset of X-linked lymphoproliferative disease due to SAP deficiency is childhood. Age of onset can vary across affected individuals.