Most types of SCID are considered typical SCID, characterized by low or no T cells and a non-functional immune system.

The exceptions to typical SCID are leaky SCID and Omenn Syndrome. Leaky SCID occurs when the defect in a gene allows for a normal, or even elevated, T cell count, which harms the immune system. Omenn Syndrome is characterized by defects in genes that cause high numbers of non-working T cells, and a lack of B cells resulting in a faulty immune system.

The treatment approach will vary with the SCID types so it’s important to know what kind of SCID is affecting the child.

Typical SCID

The most common types of typical SCID are: X-linked SCID, ADA SCID, RAG-1 or RAG-2 SCID, and IL7R SCID.

X-linked SCID is caused by mutations on the X chromosome, and generally only occurs in boys.

All of the other types of SCID are so-called autosomal recessive forms of SCID, meaning the mutations are on the other chromosomes. These forms of SCID can affect boys and girls. In autosomal recessive SCID, the child has two incorrect copies of the particular gene in each cell.

Below is a list of all of the types of SCID, with the top four most common ones discussed first, and the remaining listed in alphabetical order

X-linked SCID

(T cell negative, B cell positive)

X-linked SCID is the most common form of SCID. Of all SCID cases, about 40% are X-linked. X-linked SCID generally only affects boys. Girls can be carriers of X-linked SCID but they won’t be affected.

X-linked SCID is caused by mutations in the IL2RG gene. The IL2RG gene tells the cells to make proteins that help immune cells to grow. Without these cells, the child with SCID will contract an infection quickly. X-linked SCID is characterized by very low T cells and non-functional B cells.

X-linked SCID is called X-linked SCID because the mutation of the gene is on the X chromosome. This means that much of the time, the disease is passed from mother to son. However, it can occur spontaneously; in other words, it can occur without the mother being a carrier.

A male with X-linked SCID will pass the gene along to his daughters, who will be carriers. He will not pass the gene to his sons. A female who is a carrier has a 50% chance of passing it along to daughters (who will then be carriers) and to sons (who will then have the disease).

Adenosine deaminase deficiency or ADA SCID

(T cell negative, B cell negative)

Adenosine Deaminase Deficiency, or ADA, SCID is the second most common type of SCID, accounting for about 15% of cases.

Normally, the ADA enzyme would eliminate a molecule called deoxyadenosine, generated when DNA is broken down. ADA converts deoxyadenosine, which is harmful, to a different molecule which is harmless.

When there is no ADA to convert the harmful deoxyadenosine, the deoxyadenosine builds up in the child’s system, and kills the immune system cells.

Lack of the ADA enzyme also leads to neurological problems such as cognitive impairment, hearing and visual impairment, low muscle tone, and movement disorders.

The neurological problems are not fully curable by hematopoietic stem cell transplantation, also known as a bone marrow transplant.

RAG-1 and RAG-2 deficiency SCID

(T cell negative, B cell negative)

Deficiencies in the RAG genes represent the third most common type of SCID. There can be mutations in either or both of the RAG-1 and RAG-2 genes.

The RAG-1 and RAG-2 deficiencies have also been found to cause Omenn Syndrome more often than other types of SCID. In Omenn Syndrome, abnormal T cells attack the body’s other cells.

IL7R deficiency SCID

(T cell negative, B cell positive)

The fourth most common type of SCID is IL7R (interleukin 7 receptor) deficiency. In this type of SCID, the defective gene prevents the creation of the IL7 receptor chain, which interrupts the signaling for the development of T cells. Children with the IL7R deficiency type of SCID have B cells but few or no T cells. Because of the lack of T cells, the B cells do not work.

Other Types of SCID

CD3 complex component deficiency SCID

(T cell negative, B cell positive)

CD3 chain deficiency SCID comprises three other forms of SCID: CD3D, CD3E and CD247, also known as CD3Z. These forms of SCID are due to mutations in the genes that encode three of the individual protein chains that make up a part of the molecules on the surface of T cells. These molecules on the surface of the T cells are called the T cell receptor complex, or CD3. The CD3 chain deficiency results in damage to the T cells.

CD45 deficiency SCID

(T cell negative, B cell positive)

Another type of SCID is due to mutations in the gene encoding CD45, a protein found on the surface of all white cells that is necessary for T cell function.

Cernunnos-XLF deficiency SCID

(T cell negative, B cell negative)

Deficiency in the cernunnos-XLF gene is rare and is characterized by underdeveloped heads and brains, inability to grow at a normal rate, and lack of T and B cell function.

Coronin-1A deficiency SCID

(T cell negative, B cell positive)

Coronin-1A deficiency SCID causes a disruption of T cells produced by the thymus gland.

DCLRE1C or Artemis SCID or SCID A

(T cell negative, B cell negative)

Mutations in the DCLRE1C gene can cause Artemis SCID, also known as SCID A, and sometimes referred to as Athabascan-type SCID. This type of SCID is found primarily in the Navajo Nation. Mutations in the DCLRE1C gene can also cause Omenn Syndrome.

DNA ligase 4 deficiency SCID

(T cell negative, B cell negative)

This type of SCID is caused by a deficiency of DNA ligase 4 and it has a wide range of symptoms including underdeveloped heads and brains, a malformed face, failure to grow, and developmental delays, along with the lack of immune system.

DNA-PKcs deficiency SCID

(T cell negative, B cell negative)

DNA-PKcs deficiency SCID is extremely rare, and children with this disorder display the classic SCID symptoms including infections, diarrhea, and poor growth.

JAK3 deficiency SCID

(T cell negative, B cell positive)

JAK3 SCID is a deficiency in the Janus Kinase 3 gene. Because the protein made by the JAK3 gene works together with the protein made by the IL2RG gene, children with JAK3 deficient SCID have a similar lymphocyte profile characterized by low T cells. However, because the gene for JAK3 is not on the X chromosome this type of SCID can affect boys and girls.

LAT deficiency SCID

(T cell negative, B cell positive)

LAT deficiency SCID means that a child has mutations in the gene coding for linker for activation of T cells (or LAT), a molecule which plays a role in the development of T cells. LAT assists in helping T cells develop in the thymus.

Reticular dysgenesis SCID

(T cell negative, B cell negative)

Reticular dysgenesis is caused by mutations in the AK2 gene and is the most severe form of SCID. The reason why it is so severe is because not only is the child lacking in T and B cells but they are also lacking neutrophils which makes them even more susceptible to infection. Symptoms are present at birth include deafness, diarrhea, fever, sepsis, failure to thrive, infections, and abscesses.

Leaky SCID

Leaky SCID occurs when a person has symptoms similar to typical SCID, but with T cell counts that aren’t low enough to qualify as typical SCID. It’s called “leaky” because some T cells “leak” through and make a person’s blood cell count seem normal.

The T cell production doesn’t help the person fight infection, however. In leaky SCID, the T cells become over-activated and cause the body to attack itself. Leaky SCID can result in itchy skin, red skin, hair loss, enlarged liver and spleen, swollen lymph nodes, and diarrhea. It can also cause anemia and thyroid problems.

A person with leaky SCID might have a different type of gene mutation in the same gene as a person with typical SCID, such as RAG-1 and RAG-2 genes. Sometimes, children with leaky SCID don’t get diagnosed until they are older and even into adulthood.

Omenn Syndrome

Omenn Syndrome can present on its own or be caused by SCID. Genetic mutations that can cause Omenn Syndrome include RAG-1, RAG-2, adenosine deaminase deficiency (or ADA), Artemis and DNA ligase 4.

Omenn Syndrome infants suffer from a lack of an immune system as well as autoimmune activity in which the body attacks itself. Symptoms include red and peeling skin, hair loss, enlarged lymph nodes, enlarged liver and spleen.