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Inherited immune disorders

X-linked lymphoproliferative disease type 1 (XLP1)

Also called X-linked lymphoproliferative disease type 1 due to SH2D1A deficiency

If you or someone you love has just heard this diagnosis, start here. This guide explains what the condition is, how it is usually treated and where a transplant fits.

XLP1 is a rare inherited immune disorder, mostly in boys and men, caused by changes in the SH2D1A gene. It can lead to a severe inflammatory illness called HLH, often after Epstein–Barr virus infection, as well as antibody problems and lymphoma. A donor stem cell transplant is the only known cure, and results are better when it happens before HLH.

Written and source-checked by the Jada Bascom FoundationSources checked Editorial standards

In-depth guide
Other names and abbreviations

XLP1, XLP-1, SH2D1A deficiency, SAP deficiency, Duncan disease, X-linked lymphoproliferative syndrome type 1

In short

  • XLP1 is an inherited immune disorder, mainly in males. It can cause severe inflammation called HLH, antibody problems and lymphoma. Epstein-Barr virus is a key trigger.
  • Antibody (immunoglobulin) replacement and treatment for infection, HLH or lymphoma deal with current illness. They can also help prepare a person for transplant.
  • A stem cell transplant from a related or unrelated donor can correct the immune defect. It may be considered before severe illness develops.
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Underlined words open a short explanation. See all terms

Where transplant fits

can correct the underlying immune defect. Appropriate related or unrelated donors may be used, and may be considered before severe illness develops.

Treatment depends on the exact diagnosis, disease stage, prior treatment and the person’s health.

Some patients need a donor who is not a relative.

See if you can join

Key facts

Who it affects
An X-linked disorder predominantly affecting males, with variable age and severity of presentation.
How it is passed on
X-linked: the changed gene is on the X chromosome, so it mostly affects boys.
Cells used in a transplant
When transplantation is appropriate, the graft contains blood-forming stem cells from a suitable donor. Bone marrow, peripheral blood or cord blood may be selected according to the condition and transplant protocol.
Where a donor fits
Donor transplant option

The condition

What it is

XLP stands for X-linked lymphoproliferative disease. In type 1, the body lacks a working protein called SAP. Killer and natural killer cells need SAP to destroy virus-infected cells. T cells also need it to help make .

Without SAP, the immune system struggles to control some infections, especially Epstein–Barr virus (EBV). EBV can cause mononucleosis, or “mono,” and most people catch it at some point. In boys with XLP1, it can set off a life-threatening reaction instead of a passing illness. XLP1 can also cause problems in boys who have never had EBV.

About these numbers. Each one says which group of people it comes from, and the place and years where the source gives them. It describes what happened across that group, not what will happen to any one person. And a figure measured among people who had a transplant is not the same as the number of people who need one.

  • About 1 in 1 million malesEstimated frequency

    Worldwide estimate published by MedlinePlus Genetics (US National Library of Medicine); page last updated May 2021

    Read the source: Estimated frequency
Where X-linked lymphoproliferative disease type 1 (XLP1) starts in the bloodIn XLP1 the SAP protein is missing or faulty; cytotoxic T cells and natural-killer cells need it to control infections such as Epstein–Barr virus.Simplified illustration.

Marked as affected: T cells and NK (natural killer) cells.

  • Blood stem cell, In the bone marrow
    • Myeloid line
      • Red blood cells
      • Platelets
      • Granulocytes
      • Monocytes
    • Lymphoid line
      • B cells
        • Plasma cells, Develop from B cells
      • T cells, Affected
      • NK cells, Affected, Natural killer cells

What causes it

XLP1 is caused by a change in the SH2D1A gene on the X chromosome. Boys have one X chromosome, so one changed copy is enough to cause the condition. Girls have two X chromosomes and are usually healthy , although a few with symptoms have been reported.

A mother who carries the change has a 1 in 2 chance of passing it to each son. Genetic counseling helps a family learn who else may carry it, including brothers who seem well.

XLP1 is different from XIAP deficiency, which is also called XLP2. The names are similar, but the genes, symptoms and transplant risks are not the same.

How it can be inheritedIn X-linked inheritance the gene is on the X chromosome, so boys, who have only one X, can be affected by a single changed copy.Simplified illustration.
Parents
  • Mother: Carrier: one changed copy on an X chromosome
  • Father: Not affected
Their children
Each son
  • 1 in 2: Affected, Inherits his mother’s changed X
  • 1 in 2: Not affected, Inherits his mother’s working X
Each daughter
  • 1 in 2: Carrier, Inherits her mother’s changed X
  • 1 in 2: Not a carrier, Two working copies

Mostly affects boys. Girls can be carriers and are sometimes affected.

The chances are the same for each pregnancy.

The SH2D1A gene is on the X chromosome, so XLP1 mainly affects males; a few females with symptoms have been reported.

  • Changed copy of the gene
  • Working copy
  • Y chromosome, with no copy of this gene

Symptoms and effects

The three main problems are HLH, abnormal antibody levels and lymphoma. HLH is the most dangerous. It is runaway inflammation that causes high fever, a swollen liver and spleen, low blood counts and liver damage. It is often set off by a first EBV infection, but not always.

Studies differ on how many people with XLP1 have abnormal antibody levels, from about one in three to two in three. This raises the risk of infections. About one in three develop lymphoma, usually a fast-growing B-cell lymphoma that often starts in the bowel. Lymphoma can appear in childhood, even before EBV infection. Rarer problems include aplastic anemia and inflamed blood vessels.

Where X-linked lymphoproliferative disease type 1 (XLP1) can affect the bodyIn XLP1, HLH can swell the liver and spleen, and lymphoma often starts in the bowel.Simplified illustration.

A simple drawing of a body. Can be affected: liver, spleen and stomach and bowel.

Can be affected

  • Liver: during HLH
  • Spleen: during HLH
  • Stomach and bowel: lymphoma that often starts in the bowel

This shows the parts of the body the condition can affect. Most people have only some of these, and the drawing says nothing about how severe any of them will be.

Diagnosis and treatment

How XLP1 is diagnosed

Doctors often first suspect XLP1 when a boy gets very sick with Epstein–Barr virus (EBV), develops HLH or lymphoma, or has low antibody levels. A family history of XLP1 is another strong clue. To look for HLH, blood tests check blood counts, the liver, clotting and signs of inflammation, such as ferritin and soluble IL-2 receptor. A test called EBV PCR measures how much of the virus is in the blood.

A lab test called flow cytometry can show whether immune cells make the SAP protein. It can give a quick answer while gene test results are still pending. Finding a change in the SH2D1A gene confirms the diagnosis. A low count of a type of immune cell called NKT cells can support the result, but a normal count does not rule XLP1 out.

Once a family’s gene change is known, brothers and other male relatives on the mother’s side can be tested, even if they seem well. Female relatives can learn whether they are carriers, and testing during pregnancy is possible. In a large study reported in 2011, about 1 in 6 patients were first found only because of their family history.

Flow cytometry is a fast first check. The gene test is what confirms XLP1.

How it is treated

Treatment depends on what is happening. Antibody replacement, called immunoglobulin, helps prevent infections when antibody levels are low. Regular blood tests watch the amount of EBV in the blood. Rituximab, a medicine that removes B cells, the cells EBV infects, can lower EBV levels, though it can also leave antibody levels low for a long time. Lymphoma is treated with chemotherapy.

HLH is an emergency. It is treated with steroids and etoposide-based therapy, such as the HLH-94 approach. In the United States, emapalumab (Gamifant) is approved for primary HLH that does not respond to standard therapy, comes back or gets worse, or when standard therapy cannot be tolerated. These treatments can control an episode, but they do not fix the missing SAP protein.

A donor stem cell transplant is the only known cure. In a worldwide study of 91 patients, survival after transplant was much lower in those who had already had HLH, and few people survived HLH without a transplant. The authors advised transplant for everyone who has had HLH, and close watching for anyone not transplanted right away. For boys found through family testing before they are sick, many experts favor a planned, early transplant. Others note that this choice is still debated, so it is made case by case with a specialist team.

for XLP1 is being developed in laboratories and early research. It is not an approved treatment.

How X-linked lymphoproliferative disease type 1 (XLP1) can be treatedAntibody replacement and treatment for HLH or lymphoma deal with current illness, and a donor transplant is the only known cure.Simplified illustration.

Kinds of treatment described for X-linked lymphoproliferative disease type 1 (XLP1): supportive care, medicines and a donor stem cell transplant.

After diagnosis, the options described here

  • Supportive care

    Antibody replacement helps prevent infections when antibody levels are low, and blood tests watch the amount of Epstein–Barr virus.

  • Medicines

    HLH is treated with steroids and etoposide, and lymphoma with chemotherapy, but these do not fix the missing protein.

  • Donor stem cell transplant

    A donor stem cell transplant is the only known cure, and results are better when it happens before HLH.

    What a transplant involves

These are the kinds of treatment this page describes, not a plan. Which ones fit, in what order and whether they are combined differs from person to person.

When transplant specialists are usually consulted

NMDP and ASTCT guidelines recommend a transplant consultation at diagnosis for X-linked lymphoproliferative syndrome. For XLP1, GeneReviews advises that transplant be strongly considered as early in life as is feasible, especially before symptoms. An early visit gives the team time to test relatives and start a donor search.

Read the guidance

What a transplant involves

What a transplant involvesTiming and details differ by person and transplant center.Simplified illustration.
  1. Step 1

    : Finding a donor

    Relatives are tested first to see whether their tissue type (HLA) matches. If none match, the team searches donor registries and cord blood banks.

  2. Step 2

    : Conditioning

    Chemotherapy, sometimes with radiation, prepares the body for the new cells.

  3. Step 3

    : Transplant day, Day 0

    The donor’s cells are given through a vein, like a transfusion.

  4. Step 4

    : Engraftment

    The new cells settle in the marrow and start making blood cells, usually within weeks.

  5. Step 5

    : Recovery

    The immune system rebuilds over months. The team watches for infection, graft-versus-host disease (donor immune cells attacking the body) and relapse.

A transplant, step by step

Daily life and the donor’s role

Living with the condition

Some families learn about XLP1 only after a son becomes very ill with EBV or HLH. Others find out through a relative’s diagnosis while their son is still healthy. Either way, families may face fast decisions about testing, treatment and transplant.

Boys waiting for a transplant may need regular antibody infusions and blood tests that watch for EBV. After transplant, families face months of close follow-up for infection, and immune recovery. In the 2011 study, the large majority of patients had good immune recovery after transplant.

Mothers who learn they are carriers may have hard questions about other children and future pregnancies. Genetic counseling and support groups for primary immune disorders can help.

The donor’s role

A transplant for XLP1 uses from another person. A matched brother can be a donor only if testing shows he does not have XLP1. Other relatives who might donate are also tested for the family’s gene change.

When there is no suitable family donor, a well-matched unrelated volunteer from a registry or donated can be used. (haploidentical) family donors are another option at some centers. Because results are better when transplant happens before HLH, a donor search can begin soon after diagnosis.

Registering as a donor cannot guarantee a match for any one boy. It helps make an unrelated donor available when time matters.

Where transplant cells come fromWhich source a team considers depends on the condition, the person and who is available.Simplified illustration.

Highlighted here: a relative, an unrelated volunteer and donated cord blood.

  • The person’s own cells

    Autologous transplant, no donor

    Collected from the person before treatment, then given back.

  • A relative

    Donor transplant (allogeneic)

    A brother or sister may be a full match. Parents and children can be half-matched donors.

  • An unrelated volunteer

    Donor transplant (allogeneic)

    Found through a donor registry.

  • Donated cord blood

    Donor transplant (allogeneic)

    Collected from a baby’s umbilical cord after birth and stored in a public bank.

Some patients rely on a volunteer donor they have never met. Joining your country’s registry could make you that person for someone.

Join the registry

Finding a donor and the outlook

How a donor is found

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

What a match meansDoctors compare tissue-type markers called HLA. Each person has two copies of each HLA gene, one from each parent.Simplified illustration.

  • 8 of 8

    All eight markers match. Doctors call this a full match.

    8 of 8: the donor matches the patient at all eight markers, two each for HLA-A, HLA-B, HLA-C and HLA-DRB1.

  • 7 of 8

    One marker differs. Some transplants use a donor like this.

    7 of 8: the donor matches at seven of the eight markers. One HLA-C marker differs.

  • Half-matched

    One set, inherited together from one parent, matches. The rest may or may not.

    Half-matched: the donor matches the four markers the patient inherited from one parent. The other four may or may not match.

  • Matches
  • Differs
  • May or may not match
  • Top row: from one parent. Bottom row: from the other.
  • DR means HLA-DRB1

Doctors can look at up to 12 HLA markers, and usually aim to match 8 to 10 of them. This drawing shows the 8 that transplant guidelines count, and it reads each one as simply matching or not.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

Looking ahead

Outlook for XLP1

In published studies, the biggest factor in XLP1 is whether a boy has had HLH. Whether and when he has a transplant matters too. Boys found through family testing and transplanted before any illness have done especially well.

In a worldwide study of 91 patients reported in 2011, all 27 transplanted patients who had never had HLH survived the transplant. Of the 48 who were never transplanted, 30 were alive when the data were collected, most of them on antibody replacement. But very few survived HLH without a transplant. A small number of people have lived into mid-adulthood without a transplant. In that study, one man was still well at 46. Even so, serious problems can still appear later in life.

An older registry, reported in 1995, found that 70% of boys with XLP died before age 10. Survival has improved since then, most likely because treatment for HLH and lymphoma has gotten better. Numbers from studies describe groups of patients, not what will happen to any one boy.

About these numbers. They describe groups of people, not what will happen to any one person.

These figures come from small groups treated at expert centers, often years ago. They show that timing matters, not what will happen to one child.

Common questions

What is the life expectancy for someone with XLP1?

There is no single number. Outlook depends mostly on whether HLH has happened and whether a transplant is done. Boys transplanted before ever having HLH have done best, and very few survived HLH without a transplant. Some people have lived into adulthood without a transplant, but serious problems can still appear later. Older figures, from before today’s treatments for HLH and lymphoma, look much worse. The outlook section on this page gives the figures, with the groups they describe.

Can XLP1 be cured?

A donor stem cell transplant (allogeneic transplant) is the only known cure. It replaces the blood-forming system with donor cells that make working SAP protein. Other treatments, such as antibody replacement or treatment for HLH and lymphoma, manage the illness but do not fix the missing protein. Adding a working SH2D1A gene to cells has restored SAP in laboratory studies of mouse and patient cells. That work is still in the lab, and gene therapy is not an approved treatment for XLP1.

Should a boy with XLP1 but no symptoms have a transplant?

This is a hard choice, and experts do not fully agree. GeneReviews says transplant should be strongly considered as early in life as is feasible, especially before symptoms. In a 2022 study of 22 boys in Japan, the UK and the US, those without symptoms before transplant did better than those with symptoms. The outlook section on this page gives the figures. Others point out that every transplant carries some risk, and that a few adults have done well without one. Families weigh this with their transplant team.

Can girls get XLP1?

XLP1 mainly affects boys and men because the SH2D1A gene is on the X chromosome. Girls have two X chromosomes, so a working copy usually protects them, and carriers rarely have symptoms. In rare cases, a girl’s body mostly uses the X chromosome with the gene change, and she can develop symptoms. A mother who carries the change has a 1 in 2 chance of passing it on in each pregnancy. Once the family’s change is known, genetic testing can show which female relatives are carriers.

Is XLP1 the same as Duncan disease or Purtilo syndrome?

Duncan disease and Purtilo syndrome are other names for X-linked lymphoproliferative disease (XLP). Today doctors split XLP into two types by the gene involved. XLP1 is caused by changes in the SH2D1A gene. XLP2, also called XIAP deficiency, is caused by changes in the XIAP gene. The two can look alike at first, but they differ in lymphoma risk, bowel disease and transplant risks. A gene test tells them apart.

Can an unrelated donor be used for a boy with XLP1?

Yes. When no brother or other relative is a suitable match, a well-matched unrelated volunteer or donated cord blood can be used. European transplant guidelines for inherited immune disorders say results with matched unrelated donors now come close to those with matched brothers and sisters. Relatives are tested for the gene change before they donate, because a brother who seems healthy may have XLP1 too. One published case describes a well boy, found because a cousin had XLP1, who had a transplant from a fully matched unrelated donor at 20 months old. He was doing well 2 years later.

Why the details matter

Someone with XLP1 who seems well can still face serious problems later.

For your next appointment

X-linked lymphoproliferative disease type 1 (XLP1)

From the Jada Bascom Foundation disease library, jadabascomfoundation.org. Printed .

Questions to bring to your care team

  • Which of his brothers and other male relatives on my side of the family should be tested for our gene change, and how soon?
  • He has not had HLH. What are the risks of waiting compared with planning a transplant now?
  • How often will you check his antibody levels and the Epstein–Barr virus in his blood while we wait?
  • Should his sisters or I be tested to see if we are carriers, and what would that mean for future pregnancies?
  • What is the exact name of the diagnosis or subtype, and what does it mean for treatment?
  • What is the goal of each treatment you are suggesting?
  • Should brothers and sisters have HLA typing, and when does a donor search start?
  • What happens if a fully matched donor is not found?
  • Where can our family find support during treatment?

A one-page list to take to the next appointment, with room for notes.

Supporting someone with a diagnosis

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Support for patients and families

These independent organizations offer information and support. JBF is not affiliated with them.

Sources and further reading

  1. X-Linked Lymphoproliferative Disease
    GeneReviews, University of Washington / NCBI Bookshelf, Accessed 2026-09-05
  2. Guidelines for hematopoietic stem cell transplantation for inborn errors of immunity
    EBMT / ESID Inborn Errors Working Party, 2021
  3. X-linked lymphoproliferative disease
    MedlinePlus Genetics, US National Library of Medicine, Last updated 2021-05-17; accessed 2026-09-24
  4. X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease
    Blood (American Society of Hematology), 2011-01-06
  5. X-linked lymphoproliferative disease type 1: a clinical and genetic update
    Frontiers in Immunology, 2025-06-12
  6. X-linked lymphoproliferative (XLP) syndromes 1 and 2
    Immune Deficiency Foundation, Accessed 2026-09-24
  7. Haematopoietic Stem Cell Transplantation for Primary Haemophagocytic Lymphohistiocytosis
    Frontiers in Pediatrics, 2019-10-25
  8. FDA approves emapalumab for hemophagocytic lymphohistiocytosis
    FDA, 2018-11-20
  9. Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency)
    Blood (Pachlopnik Schmid et al.), 2011-02-03
  10. Join the registry
    NMDP, Accessed 2026-09-24
  11. On modeling human leukocyte antigen-identical sibling match probability for allogeneic hematopoietic cell transplantation
    Biology of Blood and Marrow Transplantation, March 2016
  12. Stem Cell and Bone Marrow Transplants for Cancer
    NCI, Accessed 2026-09-24
  13. Allogeneic Hematopoietic Cell Donor Selection: Contemporary Guidelines from the NMDP/CIBMTR
    NMDP / CIBMTR, Transplantation and Cellular Therapy, 2025
  14. What is HLA? HLA basics, typing and matching
    NMDP, Accessed 2026-09-26
  15. Matching with a patient
    NMDP, Accessed 2026-09-26
  16. Using flow cytometry to screen patients for X-linked lymphoproliferative disease due to SAP deficiency and XIAP deficiency (Marsh, Bleesing, Filipovich)
    Journal of Immunological Methods, 2010
  17. Preemptive hematopoietic cell transplantation for asymptomatic patients with X-linked lymphoproliferative syndrome type 1 (Tomomasa et al.)
    Clinical Immunology, 2022-03-30
  18. Recommended timing for transplant consultation: immune deficiency diseases
    NMDP and ASTCT, Accessed 2026-09-26
  19. EBMT/ESID inborn errors working party guidelines for hematopoietic stem cell transplantation for inborn errors of immunity
    Bone Marrow Transplantation (EBMT / ESID Inborn Errors Working Party), 2021-07-05
  20. Hematopoietic cell transplantation for asymptomatic X-linked lymphoproliferative syndrome type 1 (Tamura et al.)
    Allergy, Asthma & Clinical Immunology, 2018-11-14

This information explains a condition and its treatments. It cannot diagnose an illness or recommend treatment for an individual. Your care team can explain how the evidence applies to you. Written and source-checked by the Jada Bascom Foundation. Each page lists the published sources it draws on.

Ways to help

Someone may be waiting for a match.

Some people with X-linked lymphoproliferative disease type 1 (XLP1) are treated with a transplant from a donor. When no relative matches, that donor is often a stranger who joined a registry.

Join the registry

JBF points you to the official registry that serves your country. It explains who can join and what donation involves.

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Help someone you love find a donor

If someone you love needs a donor, our family guide explains practical ways to help. A registration drive can add many potential donors at once, for them and for others.

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Gifts to the Jada Bascom Foundation support donor-awareness education like this page, community outreach, drive planning and referrals to official registries.

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More in the library

Keep learning

Part of Hemophagocytic lymphohistiocytosis (HLH), a guide to how the subtypes fit together.

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