Patient Education
What is severe combined immunodeficiency (SCID)?
SCID is a rare primary immunodeficiency disorder in which there is a combined absence of T-lymphocyte and B-lymphocyte function. It can lead to extremely serious infections which can even be fatal.
What is the cause of severe combined immunodeficiency?
There are currently 12 known types of SCID based on various genetic mutations. These are
- Deficiency of the common gamma chain of six different cytokine receptors - This is the commonest form of SCID and seen only in males. It has very low T-lymphocytes and NK-lymphocytes but B-lymphocyte count is high though they do not function properly.
- Adenosine Deaminase (ADA) deficiency - This type of SCID occurs due to mutation in the gene that forms ADA. ADA deficiency is the second most common cause of SCID and children have low T cells, B cells, and NK cells. Both boys and girls are affected.
- Deficiency of the Alpha Chain of the IL-7 receptor. Affected children have no T cells but have normal B cells and NK cells. However, B cells do not function properly.
- Deficiency of the Janus Kinase 3 (JAK 3) - Patients have no T & NK cells but normal B cells that do not function properly.
- Deficiencies of CD3 chains: Three types are seen
- Deficiencies of CD45
- Recombinase activating genes 1 and 2 (RAG 1 and RAG 2) deficiency. It is also known as Ommen’s syndrome. Patients have absent T & B cells but normal NK cells.
- Artemis deficiency - Patients have absent T & B cells
- Ligase 4 deficiency - Patients have absent T & B cells
There are other SCID causing mutations that have not been identified.
What are the symptoms of severe combined immunodeficiency (SCID)?
Symptoms of SCID are recurrent serious infections starting right in infancy. Infections by unusual organisms such as pneumocystis jiroveci (PCP), chickenpox, cytomegalovirus (CMV) are commonly seen. Patients commonly have serious bacterial, viral, and fungal infections and may succumb to one of the infections.
Some children may also have a rash due to a reaction caused by the mother's T cells in the baby's blood circulation leading to a reaction against the baby's organs. This is known as graft versus host disease.
The doctor will notice that in spite of serious infections, the child has no glands enlarged and tonsils are also absent (Lymph nodes and tonsils are where the lymphocytes are stored). Chest X-Ray will also show the absence of a thymus.
How is the diagnosis of severe combined immunodeficiency made?
Diagnosis of SCID is suspected by depicting low lymphocytes in the blood (usually lymphocytes are more than 4000/cumm but in SCID they are less than 1500/cumm). Diagnosis is confirmed by demonstrating low T-lymphocytes. The number of B-cells and NK cells help to classify SCID as T- B- or T-B+ SCID. The most definitive test is to examine the function of T-lymphocyte which is depressed in SCID. Immunoglobulin levels are also low in SCID.
Are there genetic tests available to diagnose severe combined immunodeficiency?
Genetic tests are available to detect specific mutations causing SCID. This helps to determine the chances of recurrence in other children and whether only boys will be affected or both boys and girls will be affected.
Is prenatal diagnosis possible for severe combined immunodeficiency?
Prenatal diagnosis for SCID can be done provided the genetic mutation causing SCID is known in a previously affected child in the family. Then in the current pregnancy, chorionic villus sampling or amniocentesis can be done and checked whether the fetus has the same mutation or not. In the case of SCID affecting only boys, if the current fetus is a female, then she would not be affected. In the case of SCID due to ADA deficiency, ADA levels can be checked in the amniotic fluid or chorionic villus cells and ADA deficiency can be ruled in or out.
What is the treatment of severe combined immunodeficiency?
SCID is a potentially fatal condition and bone marrow transplant (BMT) or gene therapy should be considered in these patients. Infact, this disease is also called as bubble boy disease based on a boy who stayed in a plastic-covered sterile environment to prevent infections. The child finally succumbed to his disease at 12 years of age. Without a bone marrow transplant, most patients succumb to a serious infection by 2 years of age.
In case BMT is not possible, immunoglobulin replacement therapy. should be given for infants more than 3 months of age. For patients with SCID due to ADA deficiency, a modified form of the enzyme (called PEG-ADA) can be given as replacement as 2 subcutaneous injections per week lifelong. Gene therapy is an emerging therapy for patients with SCID. Patients with SCID should be on Cotrimoxazole antibiotics to prevent PCP.
Infections should be treated aggressively and urgently. Patients with SCID should avoid contact with young children outside the family as they could pass infections. Siblings should receive chickenpox vaccine and injectable polio vaccine (not oral polio vaccine as they excrete live virus which could be dangerous to a patient with SCID). Siblings should also not receive the rotavirus vaccine.
Children with SCID should avoid overcrowded public places.
What precautions should be taken in a patient with severe combined immunodeficiency (SCID)?
A patient with SCID should not receive any live vaccines such as rotavirus vaccine, chickenpox vaccine, mumps vaccine, measles vaccine, oral polio vaccine or BCG vaccine. If the patient requires a blood transfusion, then irradiated (CMV-negative, leukocyte-depleted) blood should be given to prevent graft versus host disease due to T-cells in donor blood.
How does bone marrow transplantation cure severe combined immunodeficiency?
In a BMT, bone marrow cells from a donor replace lymphocytes in the patient. The ideal donor is a perfectly matched immuno-competent brother or sister.