In 1976 ,John Travolta starred in the movie "The boy in the plastic bubble" about a young man with a compromised immune system, In the movie he had to make the choice of living in isolation within his plastic bubble or dying by interacting with the outside world.
In the year 2001 the Hollywood recreated the same theme with a romantic comedy movie "Bubble boy" with Jake Gyllenhaal
Even though the Hollywood made this into a something larger than life, this theme is based on Reality. The characters compromised health is loosely based on a severe immunity disorder which result in an absence of an immunity system.
Take a look at the story of David Vetter.
This is called Severe Combined Immunodeficiency Syndrome (SCID) which is an inherited Primary Immunodeficiency Syndrome (PIDS). (4)
"SCID is often called “bubble boy disease” SCID became widely known during the 1970′s and 80′s, when the world learned of David Vetter, a boy with X-linked SCID, who lived for 12 years in a plastic, germ-free bubble."
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| Baylor College of Medicine Archives; In the past, children with SCID were isolated in a germ-free sterile clear plastic bubbles, thus the name “bubble baby disease”[Internet] [Cited 2021 June 02] Available from: https://blog.cirm.ca.gov/2017/03/29/bye-bye-bubble-baby-disease-promising-results-from-stem-cell-gene-therapy-trial-for-scid/ |
SCID is characterized by a block in T lymphocyte differentiation that is variably associated with abnormal development of other lymphocyte lineages like B cells or Natural Killer cells. So simply in SCID neither the T cells nor the B cells work properly. (1)
When the B cells are not working the babies with SCID can't produce antibodies. So once the antibodies that comes from mother are gone, they easily get the types of infections that antibodies are good at preventing.
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| Picture showing the difference between a normal human and a diseased human[Internet] [Cited 2021 June 02] Available from: https://hubpages.com/health/Severe-Combined-Immunodeficiency-SCID |
Symptoms of SCID
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| Duke University from the Maternal and Child Health Bureau of the Health and Resources and Services Administration [Internet] 2009 April 29 [Cited 2021 June 02] Available from: https://www.hrsa.gov/sites/default/files/hrsa/advisory-committees/heritable-disorders/rusp/previous-nominations/scid-27-june-2018.pdf |
Symptom Timing
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| Duke University from the Maternal and Child Health Bureau of the Health and Resources and Services Administration[Internet] 2009 April 29 [Cited 2021 June 02] Available from: https://www.hrsa.gov/sites/default/files/hrsa/advisory-committees/heritable-disorders/rusp/previous-nominations/scid-27-june-2018.pdf |
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| Warren J. Leonard,Chapter 15 - Severe Combined Immunodeficiency as Diseases of Defective Cytokine Signaling,[Internet]Primary Immunodeficiency Disorders,Academic Press,2014,Pages 181-196, [Cited 2021 June 03] Available from:https://www.sciencedirect.com/science/article/pii/B9780124071797000151 |
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| [Cited 2021 June 02] Available from: http://acronymsandslang.com/acronym_image/81/d36b1389252eef7ce32274fe98c82873.jpg |
X-linked SCID
X-linked SCID (SCID-X) accounts for 50–60% of cases of SCID. This X-SCID is characterized by an absence of mature T and Natural Killer lymphocytes and B cells have normal phenotype and are present in increased number.(1)
X-SCID has an X-linked or autosomal recessive inheritance that results in phenotype expression predominantly in males. (9)
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| Fischer, A., Notarangelo, L., Neven, B. et al. Severe combined immunodeficiencies and related disorders.[Internet] (2015) [Cited 2021 June 02] Available from: https://www.nature.com/articles/nrdp201561?WT.feed_name=subjects_bone-marrow-transplantation#citeas |
Histologically;
- The thymus lacks a cortex/medullar differentiation
- Lymphoid precursors are scare
- Hassal's corpuscles are not detectable(6)
- Peripheral lymphoid organs are also hypoplastic
indicating the block on the T cell differentiation pathway.(1)
Reason
It was found that mutation in the common gamma chain in the X chromosome is responsible for X-SCID because all patients with X-SCID had the γc mutation.(5)
The SCID-X1 locus was mapped to Xq12-13.1 (5)
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| [Cited 2021 June 02] Available from: https://www.slideshare.net/khawajamahnoor/severe-combined-immunodeficiency-48151749 |
γc is a member not only of the IL-2 receptor but also of the IL-4, IL-7, IL-9, and IL-15 receptors. (7)
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| Burns S.,HPV infections in X-SCID patients [Cited 2021 June 02] Available from: https://www.ucl.ac.uk/immunity-transplantation/research/immunodeficiency/hpv-infections-x-scid-patients |
Genetics and Inheritance
X-SCID is inherited in an X linked manner. If the mother of the family is a heterozygote (carrier), the chance of transmitting the mutated gene is 50%. Males who inherit the mutated variant will be affected and females will be the carriers and will not be affected. Males with X-SCID will pass the mutated gene to their daughters and one of their sons. (3)
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| X-linked recessive inheritance [Cited 2021 June 02] Available from: https://en.wikipedia.org/wiki/X-linked_recessive_inheritance |
Diagnosing
If there is a family history, a screening for X-SCID is done. (3)
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| Catharine M, Haddad E, Issekutz T, et al. Newborn screening for severe combined immunodeficiency: a primer for clinicians[Internet] 2017 Dec. 18 [Cited 2021 June 03] Available from: https://www.sciencedirect.com/science/article/abs/pii/S0091674913006714 |
And if there is no family history of X-SCID and prior to newborn Screening for X-SCID, most baby boys comes to medical attention between age three to six months because;
- Their failure to thrive
- Oral/diaper candidiasis
- Absent tonsils and lymph nodes
- Recurrent infections
- Infections with opportunistic organisms such as Pneumocystis
- Persistence of infections despite conventional treatment.(3)
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| Chawdry S. Symptoms and signs of bubble baby disease [Cited 2021 June 02] Available from: https://www.medindia.net/patientinfo/symptoms-and-signs-of-bubble-baby-disease.htm |
Additional common features include;
- Rashes
- Diarrhea
- Cough and congestion
- Fevers
- Pneumonia
- Sepsis
- Other severe bacterial infections.(3)
Treatment
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| Encyclopædia Britannica, Inc, Bone Marrow [Cited 2021 June 02] Available from: https://www.britannica.com/science/bone-marrow-transplant |
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| Breaking Out of the Bubble 2019 June 10 [Cited 2021 June 02] Available from: https://bionest.com/breaking-out-of-the-bubble/ |
Over the past decade, scientists worldwide have developed new treatments by introducing a correct copy of the IL2RG-cDNA.
Gene therapy has given good results when applied to young children. But in few patients the IL2RG-gene vector has caused Leukemia unfortunately.
Activation of cellular proto-oncogenes by accidental integration of the gene vector has been identified as the underlying mechanism.
In future clinical trials, improved vector technology in combination with other protocol modifications may reduce the risk of this side effect. (8)
The best timing for BMT is immediately after birth. Infants undergoing transplantation in the first 3.5 months of life have a much higher rate of survival than those undergoing transplantation later.(3)
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| Dubnicoff T. Bye Bye bubble baby disease: promising results from stem cell gene therapy trial for SCID [Internet] 2017 March 29[Cited 2021 June 02] Available from: https://blog.cirm.ca.gov/2017/03/29/bye-bye-bubble-baby-disease-promising-results-from-stem-cell-gene-therapy-trial-for-scid/ |
Between the diagnosing and the treatment managing includes;
- Treatment of infections
- Immunoglobulin infusions and prophylatic antibiotics (particularly against Pneumocystis jirovecii)
- Isolation from Cytomegalovirus (CMV) exposures.
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| Slidetodoc [Internet] [Cited 2021 June 03] Available from; https://slidetodoc.com/biotechnology-biotechnology-terms-gel-electrophoresis-dna-fingerprint-transgenic/ |
Surveillance
After a successful bone marrow transplant The babies should be under constant monitoring of their growth, immune and lung function and also gastrointestinal and dermatologic findings should be reported every 6 to 12 months.(3)
Agents/circumstances to avoid
- Live vaccines
- Transfusion of non-irradiated blood products
- Breast-feeding and breast milk
- Exposure to young children
- Sick contacts
- Individuals with cold sores(3)
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| Shutterstock [Internet] 2017 Sept. 25 [Cited 2021 June 02] Available from: https://blog.frontiersin.org/2017/09/25/frontiers-in-immunology-scid-baby-infant-immune-deficiency-pediatrics/ |
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