What Is X-Linked Lymphoproliferative Disease 1 (XLP1)?

X-linked lymphoproliferative disease 1 (XLP1) is a type of X-linked lymphoproliferative disease. XLP is a rare genetic condition that causes the immune system to overreact to the Epstein-Barr virus (EBV) infection. It causes a severe inflammatory syndrome called hemophagocytic lymphohistiocytosis (HLH). XLP1 patients are also more likely to develop lymphomas or low antibody levels, which can cause repeated or serious infections. Only about 1 male in 1 million has XLP1.

XLP1 Causes

XLP1 is caused by a change in the SH2D1A gene. The SH2D1A gene is responsible for coding the SAP protein. The body needs the SAP protein to control the immune system. People with XLP1 have problems with the SAP protein or they do not have the protein at all. Another name for XLP1 is SAP deficiency.

The genetic change that causes XLP1 is on the X chromosome. Boys have one X chromosome and one Y chromosome. They develop XLP when they have a changed copy of the SH2D1A gene on their X chromosome.

Girls have two X chromosomes. They would need to have a changed copy of the SH2D1A gene on both X chromosomes to get XLP1. This almost never happens. But, girls can be carriers of the genetic change. This means they can pass it along to their children.

XLP1 Signs, Symptoms and Other Problems

XLP1 symptoms can vary from person to person. In general, people with this condition are at increased risk for these three health conditions:

• Hemophagocytic lymphohistiocytosis (HLH), a rare disorder of the immune system that causes organ damage (usually triggered by infection with EBV)
• Lymphoma, a type of blood cancer
• Hypogammaglobulinemia, lower than normal levels of proteins called antibodies

Not everyone with XLP1 will have all three of these conditions. It is not clear why some people get them while others do not. A person can have one of these conditions and not the others.

Children with XLP1 also can develop:

• An abnormal immune system response to EBV
• Aplastic anemia (bone marrow failure)
• Vasculitis (small blood vessel inflammation)

XLP1 and Hemophagocytic Lymphohistiocytosis (HLH)

About half of the children who have XLP1 develop hemophagocytic lymphohistiocytosis (HLH). HLH in patients with XLP1 is usually triggered by EBV infection. HLH causes uncontrolled inflammation. It damages organs in the body and can be life-threatening. Signs and symptoms of HLH include:

• Swollen lymph nodes (glands in the neck, under the arm or in the groin)
• Enlarged liver and spleen
• Liver, heart, spleen and kidney damage
• Fever
• Skin rash
• Jaundice (yellowing of the eyes and skin)
• Bone marrow problems
• Anemia (not enough healthy red blood cells)
• Thrombocytopenia (low platelets)
• Neutropenia (low neutrophils)
• Digestive problems, such as problems absorbing nutrients

XLP1 and Lymphoma

About 20% to 30% of patients with XLP1 develop lymphoma. This is a cancer that affects immune cells called lymphocytes. Most of the time, in children with XLP1, lymphoma develops after a child is infected with the Epstein-Barr virus. Signs and symptoms of lymphoma include:

• Fever
• Fatigue
• Lack of appetite and weight loss
• Enlarged lymph nodes

XLP1 and Hypogammaglobulinemia

One-third to two-thirds of children with XLP1 develop hypogammaglobulinemia. This condition causes lower than normal levels of proteins called antibodies. Signs and symptoms include:

• Repeated or serious infections
• Cough
• Cold symptoms
• Stomach problems

XLP1 Diagnosis

If your child’s doctor is concerned that your child may have XLP1, the first step after a physical exam and symptom check is to do a blood test. Your doctor may test your child’s blood for “SAP protein level.” If the tests show little to no SAP protein that may mean that the child has XLP1.This means genetic testing should be done.

Your doctor may order a genetic test to diagnose XLP1 with or without doing the “SAP protein level” test. Genetic testing is the best way to diagnosis XLP1. Your doctor may also test your child’s bone marrow to check for signs of XLP1 or cancer.

XLP1 Treatment

At this time, the only cure for XLP1 is allogeneic hematopoietic stem cell transplantation (bone marrow transplant with blood-forming stem cells).

If your child has X-linked lymphoproliferative disease 1, the care team will focus on providing therapies that regulate the immune system. Treatment for XLP1 can include:

• Antibiotics to prevent infection
• Immunoglobulin (a type of antibody) to help the immune system work better
• Steroids
• Chemotherapy
• Immune suppressant drugs

Children with XLP1 need ongoing care from an experienced team of specialists. These specialists will work to find problems early so that treatment can help minimize the effects of this disease. For example, if your child develops lymphoma, they will need to have standard cancer treatment. If your child develops hypogammaglobulinemia, treatment may involve infusions to treat low antibody levels.

Children with XLP1 should not have live virus vaccines because of their abnormal immune system. These include rotavirus; chickenpox/varicella; and measles, mumps and rubella (MMR).