Primary Immunodeficiencies (PIDs), Primary Immune Regulatory Disorders (PIRDs) and White Blood Cell Disorders

Primary Immunodeficiencies (PIDs), Primary Immune Regulatory Disorders (PIRDs) and White Blood Cell Disorders

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At MSK Kids, children with rare blood disorders are cared for by world-renowned experts who are committed to quality of life.

If your child’s doctor talked with you about pediatric immunodeficiencies or primary immune deficiencies, MSK Kids has helpful information about these disorders. We understand that this may be a scary diagnosis for your child and family. You may have to make some difficult decisions. We offer information to describe the causes and symptoms of pediatric immunodeficiencies and white blood cell disorders.

We also explain treatment options available at MSK Kids for these conditions. Please reach out to us to learn more about our services for pediatric immunodeficiencies.

There are several types of immunodeficiencies, also known as immune disorders or immune deficiencies. These rare genetic disorders that prevent the body from having the right immune response to fight an infection.

Disorders of the immune system may make your child more likely to get infections.

  • Severe combined immunodeficiency (SCID) is a genetic disorder, which means it’s caused by mutations (changes) in genes. It affects infection-fighting immune cells. Children with SCID are very likely to get severe infections.
  • Primary immunodeficiencies (PIDs) lower the number of immune cells, which fight infection. This makes it harder for your child’s body to fight infections.
  • Primary immune regulatory disorders (PIRDs) can make your child’s immune system overactive. This makes it more likely they get an inflammatory or autoimmune disorder.

At MSK Kids, our pediatric hematologists (doctors who specializes in blood disorders) care for children with immune disorders. We can treat even the rarest PIDs and PIRDs and have long been a leader in the care of people with SCID. In 1973, Memorial Sloan Kettering Cancer Center performed one of the first bone marrow transplants in the world to treat this disorder.

Today, MSK Kids continues to offer stem cell transplantation for SCID and other immunodeficiencies. Treatments include gene therapy, a method that uses genes to treat or prevent disease. We also offer cellular therapy, treatment that involves changing cells to fight disease. We offer these new treatments through our research studies, also known as clinical trials. Our team will test your child to identify the roots of their immune disorder and then design the best care plan.

Why Should I Choose MSK Kids?

Cancer and immunodeficiencies have something important in common. They are both disorders of the cells. MSK experts have deep knowledge about how cancer affects cells. That knowledge greatly increases their understanding of how to treat other cellular disorders, including immunodeficiencies.

A History of Leadership

We understand it can be upsetting to come to a children’s cancer center to treat a disorder that is not cancer. MSK Kids was a founding member of the Primary Immune Deficiency Treatment Consortium. This group of more than 45 centers in North America has a shared goal. We’re committed to improving outcomes for people with rare, life-threatening, inherited diseases of the immune system.

Onsite Resources

We are pioneers in treating pediatric immunodeficiencies and blood cell disorders. That’s why we have many resources right here at MSK to help us study and treat this condition. We can study the genomics (all the genes) of each child’s disorder and identify possible causes. These on-site tests let us understand your child’s disease better.

Access to Clinical Trials

Clinical trials are research studies that test new treatments to see how well they work. Almost every cancer treatment given to patients was first tested during a clinical trial. Our researchers are working on new ways to reduce side effects from stem cell transplantation in infants and young people. MSK also is working on new treatments, such as gene therapy. This method uses genes to treat or prevent disease.

MSK is one of the few centers in our region that is evaluating how well adoptive T-cell therapies work. With this type of immunotherapy, a type of immune cell called T cells are given to a patient to help the body fight diseases. After transplantation, this treatment trains the immune system to fight viral infections, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Your child’s care team can talk with you about current clinical trials. Learn about our current clinical trials.

Cancer Monitoring and Treatment

Some immunodeficiencies raise the risk of certain cancers. We’re on the lookout for those diseases, too, in a process called surveillance (monitoring). Through surveillance, we can find cancer early, when it’s easier to treat.

Primary Immunodeficiencies and Primary Immune Regulatory Disorders

A primary immunodeficiency (PID) is a condition where there are low numbers of immune cells, or none at all. Immune cells include T cells and B cells, which are important white blood cells for immunity. Primary immune deficiencies are genetic disorders that can have more than 350 different genetic causes. Symptoms usually appear very early in a child’s life. You can learn more about some of the primary immune deficiencies we treat:

CD40 Ligand Deficiency (Hyper IgM Syndrome)

Children with inherited hyper IgM syndrome (also known as CD40 ligand deficieny), have higher than normal levels of an immune protein called immunoglobulin M (IgM). Like antibodies, immunoglobulins are immune disease-fighting proteins. There are several types of immunoglobulins, including M (IgM), G (IgG), A (IgA), and E (IgE). Children with this syndrome do not have immunoglobulins IgG, IgA, and IgE.

This primary immunodeficiency can make a child more likely to get bacterial and other infections. They can get infections of the eyes, respiratory tract (airways where air passes during breathing), middle ear, and skin, among other locations. They also may have diarrhea that is chronic (keeps coming back). Other symptoms include enlarged (swollen) tonsils, liver, and spleen.

MSK Kids offers several treatments for this condition:

  • We can add intravenous immunoglobulins (IVIG) — that is, through an IV or injection.
  • We can give injections with a drug called G-CSF to boost white blood cell counts.
  • We can use antibiotics to prevent pneumonia.

No matter which treatment we recommend, we monitor all children for non-Hodgkin lymphoma, a cancer that starts in the white blood cells. Hyper IgM puts children at higher risk for this disease.

Chronic Benign Neutropenia

Chronic benign neutropenia (CBN) is also known as chronic idiopathic neutropenia or autoimmune neutropenia. There are mild differences within these diagnoses.

Neutrophils are a type of white blood cell that fight back against infection. There are many possible causes of neutropenia, some of which may not cause the patient significant infections (thus “benign”) and may be short term and self-resolve with time. Neutropenia may happen after a child’s recent illness, infection, or change to medication, or may be caused by antibodies that attack and destroy neutrophils. We make a diagnosis of chronic benign neutropenia once we rule out more severe neutropenia conditions. In most cases, no treatment is needed. At times, antibiotics and growth factors (filgrastim) may be considered.

Chronic Granulomatous Disease (CGD)

Chronic granulomatous disease (CGD) is a rare inherited disorder that results in low levels of phagocytes — a type of white blood cell called neutrophils that engulf foreign bodies such as bacteria and fungi, eating and digesting them and keeping them from causing harm. Children who have low phagocyte levels due to CGD are more prone to bacterial and fungal infections. They may also develop “granulomas” — areas of inflamed tissue — most often in the digestive and urinary tracts. They may be prone to abscesses (tender masses), swollen lymph nodes, persistent diarrhea, and a chronic runny nose.

The most common treatments for CGD are antibiotic and antifungal medications to treat and prevent infections. Some children benefit from treatment with injections of a medication called interferon gamma-1b, which can reduce the frequency of severe infections by boosting the body’s immune response against infection. For severe cases not helped by medication, MSK Kids offers stem cell transplantation, the only cure for CGD.

Common Variable Immunodeficiency (CVID) or Combined Immunodeficiency (CID)

Common variable immunodeficiency (CVID) causes low levels of immunoglobulins (Ig). Like antibodies, immunoglobulins are immune disease-fighting proteins. This disorder makes people more likely to get infections, especially in the sinuses, lungs, and digestive system. About 1 in every 3 people with CVID has a genetic mutation that causes this primary immunodeficiency.

MSK Kids offers Ig replacement therapy, a treatment that boosts immunity so that infections don’t happen as often. Since CVID has been associated with changes in many different genes, our clinical genetics team has developed state-of-the-art testing to identify the particular change that might be driving CVID in each individual patient. This allows us to consider what might develop down the road and assist with individualizing the care of each child. Certain CVID syndromes may be associated with auto- or hyper-inflammatory syndromes, while others may have a higher risk of developing cancer. For each of these syndromes, we will gather all important diagnostic information and will tailor a treatment approach for each patient. These can include immune modulation, immunoglobulin replacement, cell and/or gene therapy, or hematopoietic stem cell transplantation.

Cyclic Neutropenia

In children with cyclic neutropenia — a rare disorder that may be inherited or acquired later in life — the level of white blood cells called neutrophils fluctuates and sometimes drops to very low levels. When the number of neutrophils is too low, your child may experience infections, including fever, skin infections, mouth sores, and sore throat. Sometimes we can treat these infections with antibiotics. When your child’s neutrophil count is too low, we may prescribe a drug called G-CSF (granulocyte colony-stimulating factor) to boost white blood cell counts. This medicine makes the bone marrow produce blood stem cells that mature into functioning white blood cells. In severe cases when medical treatment is not sufficient, a child may be a candidate for a stem cell transplant.

Leukocyte Adhesion Deficiency (LAD)

Leukocytes are a type of white blood cell. In children with leukocyte adhesion deficiency (LAD), a rare inherited primary immune deficiency, leukocytes lack a certain protein on their surfaces that they need to work properly. As a result, they cannot fight off bacteria and other invaders the way healthy leukocytes do, and children are prone to infections. Children with leukocyte adhesion deficiency may have gum, skin, and muscle infections and slow-healing wounds.

If your child has leukocyte adhesion deficiency, we may prescribe antibiotic treatments, sometimes continuously, to prevent infections. Your child may also have periodic transfusions of healthy white blood cells called granulocytes. We treat severe leukocyte adhesion deficiency with a stem cell transplant from a donor. This is the only known cure for this disorder and a lifesaving treatment for young children who cannot be helped with medication and transfusions alone. Your MSK Kids team will let you know the best course of care for your child.

Myeloperoxidase Deficiency (MPO Deficiency)

Myeloperoxidase is an enzyme that helps white blood cells called neutrophils fight off bacteria and other causes of infection. An inherited deficiency in myeloperoxidase is fairly common and rarely causes problems unless someone is also diabetic. Children with diabetes and myeloperoxidase deficiency (MPO deficiency) are more prone to infections caused by bacteria and fungi. If this is the case for your child, the MSK Kids team will perform a full evaluation and make recommendations about the best treatment, which may include medications. We provide long-term care for as long as your child needs, bringing together hematologists, endocrinologists, and other healthcare providers necessary to achieve and maintain the best possible health.

Severe Combined Immunodeficiency (SCID)

Severe combined immunodeficiency (SCID) is a genetic disorder. It can make your child have a low number of T cells and B cells, or none at all. These immune cells fight against infection. Different types of immune cells, such as T cells and B cells, have their own specialized job. SCID lowers the number of normal, healthy white blood cells and other immune cells. That makes it more likely a child will get infections.

  • Diagnosis: All newborns in New York and many other states have SCID screening very soon after birth. Not every child who has a positive result actually has SCID. MSK Kids can evaluate a positive SCID screening test. We have specialized blood tests to confirm or rule out SCID.
  • Stem cell transplantation: If your child does have SCID, a stem cell transplant is the best treatment and the only cure. This is especially true when it is done early in life. The MSK Kids team has performed this procedure for decades. In this procedure, we give your child healthy stem cells from a matched donor. The cells grow and rebuild the immune and blood-forming systems so they can fight off infections normally.
    Read about our leadership in treating SCID.
  • Medical treatments: MSK Kids has treatments to control SCID symptoms in children who do not yet have a stem cell donor match. For example, adenosine deaminase deficiency (ADA deficiency) is an inherited condition that damages the immune system. It’s a common cause of SCID that we treat with medications, such as enzyme replacement therapy.
  • Investigational therapies: MSK Kids has many current or planned clinical trials to test promising treatments for SCID. For example, we have a study for infants who receive a stem cell transplant. We are looking at ways to reduce the need for chemotherapy or lessen its side effects.
Severe Congenital Neutropenia (SCN)

Severe congenital neutropenia (SCN) may also be known as Severe Chronic Neutropenia or Kostmann Syndrome. Children with SCN develop serious infections as early as infancy or later in life. This inherited disorder is caused by a genetic mutation and leads to very low levels of white blood cells called neutrophils. Severe congenital neutropenia causes skin infections, mouth ulcers, gum disease, and sinus infections, and is usually found when a child is very young.

We use a drug called granulocyte colony-stimulating factor, or G-CSF, to treat SCN. It makes the bone marrow produce blood stem cells that mature into functioning white blood cells. Memorial Sloan Kettering Cancer Center researchers developed G-CSF, which has been used around the world to raise white blood cell counts in people receiving chemotherapy. It is also effective in many children with low white blood cell counts. If your child’s SCN persists despite G-CSF treatment, we may perform a stem cell transplant.

Wiskott-Aldrich Syndrome

Children with this disorder have an increased tendency to bleed and bruise. They are more likely to get infections and have a higher risk for certain cancers, such as lymphoma (a blood cancer). This primary immunodeficiency is caused by a genetic mutation (change), and mostly affects males.

MSK Kids offers stem cell transplantation, the only cure for Wiskott-Aldrich syndrome.
Read how MSK Kids helped one patient beat Wiskott-Aldrich syndrome.

With immunoregulatory disorders, T cells are not able to work as well. T cells are a type of immune cell, and they have their own specialized job in fighting infections. Children who have immunoregulatory disorders may have trouble fighting off infections. Their immune system also may not regulate well, turning off when it is needed to work. At MSK, we treat immunoregulatory disorders such as:

Autoimmune Lymphoproliferative Syndrome (ALPS)

Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited immune disorder. Children with ALPS make too many white blood cells called lymphocytes. This causes enlargement (swelling) of the lymph nodes (lymphadenopathy), liver (hepatomegaly), and spleen (splenomegaly). Your child’s immune system may attack their body’s own tissues and blood cells, causing inflammation and low blood counts.

The MSK Kids team may treat your child with medications to control inflammation and low blood counts. Some children may benefit from stem cell transplantation.

Chediak-Higashi Syndrome

Chediak-Higashi syndrome is a rare, serious immune disorder caused by mutations (changes) in a gene called the LYST gene. It may cause a weakened immune system and many infections that are hard to shake off. Symptoms start in infancy into childhood. This disorder can cause oculocutaneous albinism (white or pink hair, skin, and iris color) and problems with blood clotting like easy bruising and bleeding. It can cause nervous system problems, such as difficulty in walking, weakness, and seizures.

Our team will evaluate your child’s symptoms and choose the best treatment. We may offer antibiotics for bacterial infections, or stem cell transplantation for some children.

Hemophagocytic Lymphohistiocytosis (HLH)

Children with hemophagocytic lymphohistiocytosis (HLH) make too many activated immune cells, called macrophages and lymphocytes, to fight infections. HLH symptoms can include an enlarged (swollen) liver or spleen, fever, fewer red blood cells, and problems with the nervous system. HLH may be caused by an inherited genetic mutation. When not inherited, it’s called acquired HLH. It can be caused by the Epstein-Barr virus (EBV) infection or another viral illness.

MSK Kids offers stem cell transplantation as a cure for inherited HLH. For people having a cord blood transplant, we’re researching new ways to make this treatment easier to tolerate. We also have other treatments, including the medication emapalumab (Gamifant®) and medications to treat or prevent infections.

Immunodysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) Syndrome

Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a rare autoimmune disease. It only affects males. Symptoms usually start during a baby’s first 6 months. A child may have severe diarrhea, skin conditions (such as erythroderma, eczema, or psoriasis), and thyroid disease (thyroiditis). Boys with IPEX syndrome have mutations in a gene called the FOXP3 gene.

The MSK Kids team treats IPEX syndrome with medications that improve your child’s immune response. Some boys may be eligible for stem cell transplantation, the only cure for IPEX syndrome.

Very Early-Onset Inflammatory Bowel Disease (IBD)

Inflammatory bowel diseases (IBDs) include ulcerative colitis and Crohn’s disease. They are autoimmune diseases, illnesses where the immune system attacks and destroys healthy body tissue. Usually, IBDs are diagnosed in adolescents or young adults. When they’re diagnosed in children under age 6, it’s called very early-onset IBD. It may not be easy to treat with standard medications. Some children with very early-onset IBD have genetic mutations (changes). These mutations are in genes for immune proteins called interleukin 10 (IL-10), or in the IL-10 receptor (IL-10R). In some cases, stem cell transplantation is indicated as a possible treatment for children with these mutations.

Our team includes MSK’s pediatric gastroenterology experts. We will evaluate your child’s symptoms, identify the cause, and choose the best treatment.

X-linked Inhibitor of Apoptosis Protein (XIAP) Deficiency

X-linked inhibitor of apoptosis protein (XIAP) deficiency is also known as X-linked lymphoproliferative (XLP) disease. It is a rare disorder that almost always only affects males. It causes the body to have too strong an immune response to a very common virus called Epstein-Barr virus (EBV). Normally, when people get EBV they recover from symptoms. Their body will still have inactive EBV in a type of white blood cell called B cells. When children with XIAP deficiency get EBV, they make too many white blood cells, called T cells, B cells, and macrophages. This building up of white blood cells is a rare disorder called hemophagocytic lymphohistiocytosis (HLH). Children may also be at higher risk for lymphomas and can have abnormal levels of immunoglobulins.

MSK Kids may treat your child for XIAP deficiency with the medications ruxolitinib (Opzelura™) or emapalumab (Gamifant®). They also may recommend stem cell transplantation.

What are the Symptoms of Immunodeficiencies in Children?

Children who have a deficiency of the immune system can get infections often. They may get ear infections, sore throats, pneumonia, diarrhea (watery stool), and fevers. They also may take longer than normal to get better from an infection. They may grow more slowly than other children. Infections in children with SCID can be serious and life-threatening. They must be treated right away.

Find Out How We Can Help Your Child

Contact us online or by phone at 833-MSK-KIDS (833-675-5437). We’ll help you set up an appointment with one of our pediatric immunodeficiency experts.