What Is Autosomal Recessive SCID?
Autosomal recessive SCID or severe combined immunodeficiency is a rare genetic disorder consisting of rare inherited conditions that result in compromised immune system functioning. It has fatal complications due to the limited or no immune response seen in those individuals affected with SCID. Even the minor infections caused by pathogens like bacteria, fungi, or viruses can produce life-threatening and severe complications in these people. Also, they share an increased risk of contracting frequent infections.
SCID is otherwise known as bubble boy syndrome.
What Are the Subdivisions of SCID?
Depending on which type of immune cell is defective, SCID is classified into the following subdivisions:
-
Classical SCID.
-
X-linked disorder (T-B+).
-
ADA SCID (T-B-).
-
RAG-1 and RAG-2 deficiency SCID (T-B-).
-
IL7R SCID (T-B+).
-
-
CD45 deficiency SCID.
-
Coronin-1A deficiency SCID.
-
Cernunnos-XLF deficiency SCID.
-
CD3 complex component deficiency SCID.
-
DNA ligase 4 deficiency SCID.
-
DCLRE1C or Artemis SCID or SCID A.
-
JAK13 deficiency SCID.
-
DNA-PKcs deficiency SCID.
-
LAT deficiency SCID.
-
Reticular dysgenesis SCID.
-
Atypical SCID.
-
Variant SCID.
How Does Our Immune System Work and What Happens in SCID?
The pathogens which enter the body, like bacteria, viruses, and fungi, are destroyed by our immune system. For which, our immune system has specialized cells called white blood cells. The white blood cells are of three types, namely,
-
B lymphocytes.
-
T lymphocytes.
-
Natural killer (NK) cells.
B lymphocytes of the body helps identify the foreign bodies by attaching themselves to these pathogens. These help point out the invaders. These are the first cells to come into action.
After the B lymphocytes have identified the pathogens, the T lymphocytes come into action. These are called the central mediators of the immune response, and they act by attacking and engulfing the pathogens. In the case of viruses, they can have a direct attack.
Natural killer cells are also a specialized type of immune cells that helps in fighting against viruses.
When there is a genetic disorder to any of the genes that affect these immune cells' effectiveness, severe combined immunodeficiency occurs. In this, almost every time, the T cells are involved, and along with it, at least one another immune cell is affected, hence the name combined immunodeficiency.
There would be fewer primary symptoms and minimal or no immune response in patients with any form of SCID. Until and unless there is an appropriate treatment, SCID cannot be managed and might lead to lethal complications.
What Causes Autosomal Recessive SCID?
Except for the X-linked classical disorder of SCID, all other types of SCID are caused by autosomal recessive inheritance, which means it can affect both genders. However, the X-linked condition affects the X-chromosome, so active diseases seen in males and females with the defective gene only act as carriers.
In the case of autosomal recessive patterns of genetic disorders, two abnormal gene copies should be obtained from each parent to develop the disease. If only one defective gene is received and another gene obtained from the parent is normal, the individual will remain unaffected. However, they are termed carriers and can inherit their genes to their offspring.
Let us discuss the causes of different types of autosomal recessive SCID.
Classical SCID:
-
ADA SCID (T-B-) - It is the most common type of SCID, next to X-linked SCID. In this type, the gene responsible for producing adenosine deaminase is defective, leading to reduced production. ADA is essential for removing the harmful deoxyadenosine from the body, building up of which damages the body's immune cells.
-
RAG-1 and RAG-2 deficiency SCID (T-B-) - In this type, there is a defect in either one or both the RAG-11 and RAG-2 genes and is the third most common type of SCID.
-
IL7R SCID (T-B+) - Interleukin 7 receptor deficiency is seen in this SCID that hinders the receptor chain of IL7, leading to reduced or no production of T cells. Lack of T cells results in a lack of work of the B cells.
-
The following table depicts the other types of SCID, and their subsequent defective gene:
What Is Omenn Syndrome?
It is another name for leaky SCID in which there is a partial defect in the RAG-1 and RAG-1 genes. As a result, there is reduced production of T cells. However, the T cells do not protect from pathogens; instead, it attacks the body's immune system due to overactivity.
What Are the Chances of Inheritance of Autosomal Recessive SCID?
When the two parents are carriers, the child has a 25 % chance of getting affected. Also, the probability of the child receiving normal genes is 25 %. At the same time, it is about 50 % for a child to be a carrier, just like the two parents.
How Is Autosomal Recessive SCID Diagnosed?
Autosomal recessive SCID is diagnosed in newborns by screening, which measures TREC (T cell receptor excision circles). When the TREC levels are low, it denotes that the number of circulating T cells in the bloodstream is low.
The number of B cells, T cells, and natural killer cells can be measured with the help of a complete blood count (CBC) together with lymphocyte subset testing.
When there are fewer immune cells detected in these tests, additional tests are performed to determine the exact cell that exhibits impaired function.
Genetic tests and biochemical or protein expression also help diagnose a few types of SCID.
How Is Autosomal Recessive SCID Treated?
For the treatment to be effective, early diagnosis is crucial. If the diagnosis is made late, aggressive treatment methods come into play. Most types of SCID cause fatal complications when diagnosed at a later stage.
1. Bone Marrow Transplantation:
It is the best available treatment method for patients with SCID. It should be done at the age of three months to be effective. Two important determinants of this treatment are the availability of a matching bone marrow donor and the type of SCID affected by the individual. If getting a suitable donor is delayed, all steps are taken to prevent infection, and it is better to avoid breastfeeding till then.
2. Gene Therapy:
Gene therapy is considered in patients for whom bone marrow transplantation is not possible; however, it is still under study.
3. Enzyme Replacement Therapy:
If the SCID is caused due to defective enzyme production like ADA (adenosine deaminase), then injecting the missing enzyme into the patient is beneficial. However, it can only provide treatment at that point and cannot cure the condition.
Conclusion:
Autosomal recessive SCID is a rare genetic condition that can be best treated by early diagnosis. If you or your partner has a family history of SCID, then talk with your healthcare provider to detect the presence of SCID at the initial stages.
