Severe Combined Immunodeficiency (SCID)

Overview

Severe Combined Immunodeficiency (SCID) is a rare, but potentially extremely dangerous Genetic immune disease which severely hampers the immune system’s ability to fight infection. Most often, it manifests at the early stages of life and is known as a primary immune deficiency that is, it results from genetic mutations inherited by the family that impact the immune system’s growth and function.

Children born with SCID are deficient in function T cells which are crucial in triggering an immune reaction. In the majority of instances, B cells as well as the Natural Killer (NK) cells are not present or inactive. Without these cells and the immune system’s function, it’s not able to effectively fight viruses, bacteria, and fungi. Even common infections could be fatal if not treated.

Causes and Genetic Basis

SCID is caused by mutations in genes that regulate the growth as well as function of the immune cell. Different genetic variations cause various types of SCID. The most frequent kind can be described as the X-linked form of SCID that is mainly affecting males. Females are able to have the defective gene, however, they do not typically suffer from symptoms since they carry a different normal X the chromosome.

Other types of inherited SCID are:

• ADA-SCID caused due to a deficiency of the enzyme adenosine deaminase (ADA)

• JAK3-SCID

• RAG1/RAG2 deficiencies

• IL7R deficiency

Certain types are inherited through some cases in an autosomal dominant pattern, which means both girls and boys can be affected in the event that two parents have the affected gene.

Signs and Symptoms of SCID

Children born with SCID usually appear healthy from birth, but start showing signs after a few months. The warning signs could include:

• Infections that are repeated and serious (pneumonia meningitis, pneumonia, sepsis)

• Chronic diarrhea

• Inability to thrive or insufficient weight gain

• Eczema-like skin rashes

• Oral Thrush that isn’t resolved

• Recurrent respiratory or ear infections

• Persistent viral infections

One of the most alarming infections among those with SCID is Pneumocystis-jirovecii pneumonia which is uncommon in healthy infants, but is common in children with immune deficiency.

Early Diagnosis is Critical

The early detection of SCID is lifesaving. In many developed nations, newborn screening for SCID is now common routine. This screening is based on the T-cell excision circle (TRECs) that are the byproducts from T cell development, in order to identify abnormalities.

In the event that SCID is suspected due to the presence of a family history or infection, blood tests are conducted to measure the level of B cells, T cells as well as NK cells. Genetic tests can determine the specific mutation responsible for. If a family has a documented background, prenatal diagnosis might also be possible.

Treatment of SCID

The most widely-accepted treatment that can cure SCID can be the transplantation of hematopoietic stem cells (HSCT), often called a bone Marrow Transplant. The procedure replaces the child’s immune system that is defective with healthy stem cells taken from an appropriate donor.

Important information regarding SCID treatment:

• The most effective results occur when HSCTs are performed within the first three months of life, prior to when infections develop.

• A Sibling donor match has the highest success rate.

• Partly or not related donors are also a possibility and often yield excellent outcomes due to better transplant methods.

Emerging Therapies

Gen therapy has been identified as an option that could be a viable alternative to certain kinds of SCID specifically the X-linked SCID as well as SCID with ADA. This method involves the patient’s bone marrow cells are genetically altered to correct the defect in immune function and then returned to the body. While it’s still primarily in clinical studies this therapy has proven positive results in the restoration of the immune system.

Other strategies for managing are:

• Prophylactic antibiotics to help prevent infections

• Immunoglobulin Replacement Therapy (IVIG) to provide passive protection against infection

• Isolation to protect in the beginning days of life

• Preventing live vaccines

Outlook and Prognosis

With the early detection and timely treatment, children suffering from SCID are able to live happy, healthy lives. In the event of delays in treatment, however could lead to irreparable infections and other complications. In countries that have newborn screening, the outcomes have significantly improved, particularly when HSCT is carried out early.

Children diagnosed by SCID are strongly urged to seek treatment at specialized transplant or immunology centers where individualized treatment plans are available.

Conclusion

Severe combined immunodeficiency (SCID) is a medical emergency that requires prompt diagnostics and treatments. While it’s rare, SCID is one of the most severe immunodeficiencies observed in infants. Transplantation of the bone marrow is the foundation of treatment and the gene therapy is an exciting and advancing research area.

Early medical intervention and specialized treatment can significantly increase the odds of long-term survival and health for children suffering from SCID.