Severe combined immunodeficiency (SCID), otherwise known as baby bubble disease, is a group of rare disorders that impact the development of infection-fighting immune cells [5]. The name stems from the past treatment of this disorder where children were “kept inside sterile plastic bubbles to keep them alive” [2].
Although appearing healthy at birth, infants are highly susceptible to severe infections and must be “kept in controlled, isolated environments”[6]. If not treated properly, a common cold or a diaper rash can prove fatal. Newborn babies begin to show symptoms before reaching six months old, including stunted growth, skin rashes, absent tonsils, and lymph nodes.
A common cause of SCID is the inherited condition of adenosine deaminase deficiency (ADA deficiency). The ADA gene is responsible for providing the ADA enzyme that is most active within lymphocytes, a type of specialized white blood cell. Lymphocytes are able to protect the immune system by “making immune proteins called antibodies or directly attacking infected cells” [3].
When mutations occur in the ADA gene, those with the deficiency are missing the ADA enzyme that is able to convert a harmful substance called deoxyadenosine into non-harmful deoxyinosine. Since the molecule is unable to be converted, it becomes toxic in lymphocytes the more it builds, resulting in chromosome breakage and inducing apoptosis [1]. This leads to premature death in lymphocytes resulting in the signs and symptoms of SCID.
Since ADA deficiency is inherited in an autosomal recessive manner, it is vital that newborns are screened for SCID. In order to display the symptoms of this condition, the mutation must be present in both copies of the ADA gene, meaning that both parents usually each carry one mutated copy of the gene. Referred to as carriers, people with only one copy of the mutation do not show any symptoms but are more likely to give birth to children with the disorder. Each child has a 25% chance of being ADA-deficient, a 50% chance of being a carrier like their parents, and a 25% chance to not have the condition or carry the mutated gene [4].
Aside from the screening, blood tests are also necessary to confirm ADA deficiency. They measure the levels of immunoglobulins and white blood cells (WBCs) including T cells, B cells, and natural killer (NK) cells, all of which play a critical role in protecting the immune system from infections. Immunoglobulins, produced by WBCs, are antibodies that bind onto certain antigens, such as bacteria and viruses, to aid in their destruction [7]. T cells, B cells, and NK cells are also similar in the way they stop infections. Consequently, a test result that yields an abnormally low level of these immune-fighting cells means that the immune system is seriously compromised.
Moving on to treatments, there are three main types that help to restore the immune system, including stem cell transplants, gene therapy, or enzyme therapy. The most effective of the three, with a 70% success rate, is the transplantation of blood-forming stem cells from a healthy sibling or family member of the affected child [4]. However, the only downside to this method is that the patient may reject the transplant; the stem cells now turning against the child.
That is why Dr. Kohn and his team at UCLA developed a therapy that “remove[s] blood stem cells from the bone marrow of … ADA-deficient SCID [patients] and genetically modifie[s] them to correct the defect” [6]. This gene-therapy stem cell treatment allows for the genetically corrected blood-forming stem cells to produce T cells that fight off infection. The immune systems of SCID patients are now restored thanks to the power of stem cells that multiply and replicate, ultimately creating a new blood supply free of the mutation.
Overall, ADA-SCID may seem like a daunting disorder at first but there are precautions put in place by healthcare professionals to provide the best care possible. It all starts with an early diagnosis that leads to much higher survival chances with prompt treatment. Ensuring that newborns are constantly monitored and that parents are tested for the mutated gene both help in the fight against immunodeficiency disorders. Now that more effective therapies are emerging, the chances for an affected patient to completely recover from ADA-SCID are higher than ever.
References
[1]Candotti, F., Moshous, D., Notarangelo, L., Villa, A., Villartay, J.P., Notarangelo, L.D. (2014). Chapter 4 - Severe Combined Immunodeficiencies. https://doi.org/10.1016/B978-0-12-405546-9.00004-2
[2]McCormack, K. (2020). Celebrating a life that almost didn’t happen. https://blog.cirm.ca.gov/tag/bubble-baby-disease
[3]MedlinePlus. (2012). Adenosine Deaminase Deficiency. https://medlineplus.gov/genetics/condition/adenosine-deaminase-deficiency
[4]NIH. (2017). Adenosine Deaminase Deficiency. https://rarediseases.info.nih.gov/diseases/5748/adenosine-deaminase-deficiency
[5]NIH. (2019). Severe combined immunodeficiency (SCID). https://niaid.nih.gov/diseases-conditions/severe-combined-immunodeficiency-scid
[6]The Cutting Edge. (2012). Bursting the Bubble of Baby Bubble Disease. https://uclahealth.org/u-magazine/bursting-the-bubble-of-bubble-baby-disease
[7]Thermofisher Scientific. (2020). Introduction to Immunoglobulins. https://thermofisher.com/ca/en/home/life-science/antibodies/antibodies-learning-center/antibodies-resource-library/antibody-methods/introduction-immunoglobulins.html
Article written by Lananh Vo
Article edited by Rachel Glantzberg
Graphics by Samantha Gu
Group advised by Ruhi Sahu