Severe combined immunodeficiency: Difference between revisions

From WikiMD's Wellness Encyclopedia

No edit summary
 
No edit summary
 
(One intermediate revision by the same user not shown)
Line 1: Line 1:
{{Short description|Genetic disorder causing severe immunodeficiency}}
{{Use dmy dates|date=March 2025}}
{{Infobox medical condition (new)
{{Infobox medical condition (new)
| name           = Severe Combined Immune Deficiency
| name = Severe Combined Immunodeficiency (SCID)
| synonyms       = '''Alymphocytosis''', '''Glanzmann–Riniker syndrome''', <br>'''Severe mixed immunodeficiency syndrome''', and<br>'''Thymic alymphoplasia'''<ref name="Bolognia">{{cite book |author1=Rapini, Ronald P. |author2=Bolognia, Jean L. |author3=Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |pages= |isbn=978-1-4160-2999-1 |oclc= |doi= |accessdate=}}</ref>
| synonyms = '''Alymphocytosis''', '''Glanzmann–Riniker syndrome''',<br>'''Severe mixed immunodeficiency syndrome''',<br>'''Thymic alymphoplasia'''
| image           =OSC_Microbio_19_04_SCID.jpg  
| image = OSC_Microbio_19_04_SCID.jpg
|alt=David Vetter, a child born in 1971 with severe combined immunodeficiency (SCID).| caption         =[[David Vetter]], a child born in 1971 with severe combined immunodeficiency (SCID).  
| alt = Microscopic image of immune cells affected by SCID
| pronounce       =  
| caption = [[David Vetter]], a child born in 1971 with SCID, famously lived in a sterile bubble.
| field           =  
| pronounce =
| symptoms       =  
| field = [[Immunology]], [[Pediatrics]], [[Medical genetics]]
| complications   =  
| symptoms = Severe, recurrent infections, failure to thrive, chronic diarrhea, pneumonia, oral candidiasis
| onset           =  
| complications = Life-threatening infections, sepsis, failure to thrive
| duration       =
| onset = Infancy
| types           =  
| duration = Lifelong (if untreated)
| causes         =  
| types = X-linked SCID, ADA-SCID, JAK3-SCID, RAG1/RAG2-SCID, IL-7Rα-SCID, etc.
| risks           =  
| causes = Genetic mutations affecting T-cell and B-cell function
| diagnosis       =  
| risks = Family history of SCID, consanguinity
| differential   =  
| diagnosis = Newborn screening (TREC test), lymphocyte count, genetic testing
| prevention     =  
| differential = Other primary immunodeficiencies, AIDS, leukemia
| treatment       =Bone marrow transplantation and prophylaxis against infection
| prevention = Genetic counseling, prenatal diagnosis
| medication     =IVIG, gene therapy  
| treatment = Bone marrow transplantation, gene therapy, enzyme replacement therapy, prophylactic antibiotics
| prognosis       =  
| medication = IVIG, gene therapy, PEG-ADA for ADA-SCID
| frequency       =1 in 50,000 to 100,000 (X-linked form)  
| prognosis = Without treatment: fatal in infancy; with treatment: improved survival
| deaths         =  
| frequency = 1 in 50,000 to 100,000 (X-linked form)
| deaths = High without early intervention
}}
}}
Severe Combined Immunodeficiency (SCID) is a rare, genetically inherited disorder that severely impairs the development and functioning of key immune cells - [[T cell]]s and [[B cell]]s. Characterized by a broad range of genetic mutations, SCID manifests with a variety of clinical presentations<ref name="five">{{cite journal |vauthors=Burg M, Gennery AR |title=Educational paper: The expanding clinical and immunological spectrum of severe combined immunodeficiency |journal=Eur J Pediatr |volume= 170 |issue=5 |pages=561–571 |year=2011 |doi=10.1007/s00431-011-1452-3 |pmid=21479529 |pmc=3078321 }}</ref>. It primarily affects the antibody response due to defects in [[B lymphocytes]] themselves or the inability of T-helper cells to correctly activate B lymphocytes<ref name="two">{{cite journal |vauthors=Aloj G, Giardano G, Valentino L, Maio F, Gallo V, Esposito T, Naddei R, Cirillo E, Pignata C |title=Severe combined immunodeficiencies: New and Old Scenarios |journal=Int Rev Immunol |volume= 31 |issue=1 |pages=43–65|year=2012 |doi=10.3109/08830185.2011.644607 |pmid=22251007 }}</ref>. This dysfunction hampers both 'arms' of the [[adaptive immune system]], owing to defects in one or more genes.
[[File:David Vetter and John R. Montgomery.JPG|David Vetter, famous SCID patient|thumb]]
'''Severe Combined Immunodeficiency''' ('''SCID''') is a rare, genetically inherited disorder characterized by profound deficiencies in both T cell and B cell function. It is considered the most severe form of primary immunodeficiency, rendering affected infants highly susceptible to life-threatening infections. The condition results from mutations in genes essential for immune system development, leading to severe immune dysfunction.


==Clinical Manifestation and Prognosis==
SCID is often referred to as the "bubble boy disease" due to the case of [[David Vetter]], who was forced to live in a sterile environment to avoid infections. Without hematopoietic stem cell transplantation (HSCT) or gene therapy, infants with SCID typically die within their first year of life due to severe infections.
Typically, SCID patients exhibit symptoms of severe bacterial, viral, or fungal infections early in life. Common presentations include interstitial lung disease, chronic diarrhea, and failure to thrive<ref name="two" />. Recurrent ear infections, [[Pneumocystis pneumonia|''Pneumocystis jirovecii'']] pneumonia, and extensive oral candidiasis are other frequent manifestations.


SCID is regarded as the most severe type of [[Primary immunodeficiency|primary immunodeficiencies]]<ref name="four">{{cite journal |vauthors=Cavazanna-Calvo M, Hacein-Bey S, Yates F, de Villartay JP, Le Deist F, Fischer A |title=Gene therapy of severe combined immunodeficiencies |journal=J Gene Med |volume=3 |issue=3 |pages=201–206 |year=2001 |doi=10.1002/1521-2254(200105/06)3:3<201::AID-JGM195>3.0.CO;2-Z |pmid=11437325 }}</ref> with at least nine different known genes whose mutations can lead to a form of SCID<ref name="six">{{cite journal |author=Buckley R |title=Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution |journal=Annu Rev Immunol |volume=22 |pages=625–655 |year=2003 |doi=10.1146/annurev.immunol.22.012703.104614 |pmid=15032591}}</ref>. SCID patients are extremely vulnerable to [[infectious diseases]]. They are often colloquially referred to as having 'bubble boy disease' or 'bubble baby disease', as their highly compromised immune system necessitates living in a near-sterile environment, much like [[David Vetter]], who gained fame for this reason.
== Causes and Pathophysiology ==
SCID is caused by mutations in various genes involved in lymphocyte development and function. It leads to severe impairments in T-cell, B-cell, and sometimes natural killer (NK) cell function.


Without treatment, typically in the form of a successful [[hematopoietic stem cell transplantation]], infants with SCID usually succumb to severe, recurrent infections within their first year of life.
=== Genetic Causes ===
There are multiple forms of SCID, each associated with mutations in different genes:
* X-linked SCID (SCID-X1) – Caused by mutations in the ''IL2RG'' gene, leading to absence of T and NK cells but presence of dysfunctional B cells.
* Adenosine Deaminase Deficiency (ADA-SCID) – Caused by mutations in the ''ADA'' gene, leading to toxic metabolite accumulation, which destroys lymphocytes.
* JAK3 Deficiency – Affects cytokine signaling and prevents normal immune cell development.
* RAG1/RAG2 Deficiency – Disrupts V(D)J recombination, preventing B and T cell receptor formation.
* IL-7Rα Deficiency – Prevents T-cell development, leading to T-cell lymphopenia.
* Other rare forms – Include defects in ''CD45'', ''ZAP70'', and ''Artemis'' genes.


==Pathophysiology==
All forms of SCID result in absent or dysfunctional T cells, which in turn affects B-cell function, leading to profound immunodeficiency.


In SCID, the [[adaptive immune system]], comprising [[B cell]]s and [[T cell]]s, is fundamentally impaired. This defect occurs due to mutations in any one of a growing number of identified genes<ref name="six"/>. These mutations disrupt the development and functioning of T cells, B cells, or both, significantly compromising the body's capacity to fight off infections.
== Symptoms and Clinical Manifestations ==
SCID presents early in infancy with symptoms such as:
* Severe, recurrent infections (bacterial, viral, fungal)
* Chronic diarrhea and failure to thrive
* Oral candidiasis (thrush)
* Persistent pneumonia, especially due to ''Pneumocystis jirovecii''
* Skin rashes (may indicate maternal T-cell engraftment)
* Absent or very small tonsils and lymph nodes


The common feature among all forms of SCID is a profound deficiency in T cell function. In some forms, B cells and natural killer (NK) cells may also be affected. For example, in X-linked SCID, one of the most common forms of the disease, the number of B cells is usually normal, but the T cells and NK cells are significantly reduced.
Without intervention, SCID is universally fatal due to overwhelming infections.


The genetic defects in SCID primarily impact the lymphocyte development, maturation, and signaling processes, leaving affected individuals with few or no functional lymphocytes. As a result, SCID patients lack almost all immune defenses, rendering them extraordinarily susceptible to infections.
== Diagnosis ==
Early diagnosis of SCID is critical for survival. Newborn screening programs, particularly the T-cell receptor excision circle (TREC) test, have dramatically improved early detection.


==Diagnosis==
Diagnostic Tests
* Complete blood count (CBC) – Shows low lymphocyte count (<3000 cells/µL).
* Flow cytometry – Identifies absence or dysfunction of T, B, and NK cells.
* Genetic testing – Identifies specific mutations causing SCID.
* Functional immune tests – Assess T-cell proliferation in response to stimuli.


Diagnosis of SCID is often suspected in infants presenting with severe recurrent infections, failure to thrive, and a history of early mortality in siblings. Diagnostic tests focus on immunological analysis, including complete blood count with differential and lymphocyte subset enumeration via flow cytometry.
Newborn Screening
* Many countries have adopted TREC-based screening, which detects low numbers of naïve T cells, allowing early intervention before infections occur.


Further genetic testing can identify the specific mutation causing SCID, which can help guide treatment decisions and offer predictive information for family planning. Prenatal and newborn screening for SCID, particularly the T-cell receptor excision circle (TREC) test, is becoming increasingly prevalent and can lead to earlier diagnosis and improved outcomes.
== Treatment ==
Without treatment, SCID is fatal. However, several treatment options restore immune function:


==Treatment==
1. Hematopoietic Stem Cell Transplantation (HSCT)
* First-line curative treatment, ideally performed before 3 months of age.
* Best outcomes occur with matched sibling donors, but alternative donors (haploidentical or unrelated) can be used.


The mainstay of SCID treatment is hematopoietic stem cell transplantation (HSCT), ideally from a matched sibling donor. This treatment can restore immune function and offers the possibility of a full cure<ref name="four"/>.
2. Gene Therapy
* Used in ADA-SCID and X-linked SCID.
* Involves correcting the patient's own stem cells using viral vectors.
* Trials show promising long-term immune restoration.


Gene therapy is another promising avenue of treatment, especially for forms of SCID caused by a single gene defect. This treatment approach involves correcting the genetic defect in the patient's own stem cells, enabling the development of functional immune cells.
3. Enzyme Replacement Therapy (For ADA-SCID)
* Pegylated adenosine deaminase (PEG-ADA) provides temporary immune support.
* Used as a bridge to definitive therapy (HSCT or gene therapy).


While waiting for definitive therapy or when definitive therapy is not possible, prophylactic antibiotics and immunoglobulin replacement therapy can be used to prevent infections. Moreover, rigorous infection control measures are crucial to protect these patients from exposure to pathogens.
4. Supportive Care
* Immunoglobulin replacement therapy (IVIG) – Prevents infections.
* Prophylactic antibiotics & antifungals – Reduces infection risk.
* Strict infection control measures – Isolation and avoidance of live vaccines.


==See also==
== Prognosis ==
The prognosis for SCID depends on early diagnosis and treatment:
* HSCT before 3 months of age – >90% survival rate.
* Late diagnosis (after severe infections occur) – Poorer outcomes.
* Untreated SCID – Death within 1–2 years due to infections.


Gene therapy holds long-term curative potential, especially for X-linked SCID and ADA-SCID.
== Epidemiology ==
* SCID affects ~1 in 50,000 to 100,000 live births.
* X-linked SCID is the most common form (~45%).
* Higher prevalence in consanguineous populations.
* Newborn screening programs have increased detection rates, leading to earlier treatment and better outcomes.
== Notable Cases ==
* [[David Vetter]] ("Bubble Boy") – Lived in a sterile plastic enclosure due to SCID, raising awareness about the disease.
* Ashanti DeSilva – First SCID patient successfully treated with gene therapy.
== See Also ==
* [[Primary immunodeficiency]]
* [[Primary immunodeficiency]]
* [[David Vetter]]
* [[Adaptive immune system]]
* [[B cell]]
* [[T cell]]
* [[Hematopoietic stem cell transplantation]]
* [[Hematopoietic stem cell transplantation]]
* [[Gene therapy]]
* [[Gene therapy]]
==References==  
* [[Adenosine deaminase deficiency]]
* [[Bubble Boy disease]]
* [[Adaptive immune system]]
 
== References ==
<references/>
<references/>


[[Category:Immunology]]
== External Links ==
{{Medical resources
| DiseasesDB = 11824
| ICD10 = {{ICD10|D|81|0|d|81}}
| ICD9 = {{ICD9|279.2}}
| OMIM = 300400
| MedlinePlus = 001248
| eMedicineSubj = ped
| eMedicineTopic = 2817
| MeshID = D007724
}}
 
{{Immunology}}
{{Rare diseases}}
{{DNA repair-deficiency disorder}} {{stub}}
 
{{DEFAULTSORT:Severe Combined Immunodeficiency}}
[[Category:Genetic disorders]]
[[Category:Genetic disorders]]
[[Category:Primary immunodeficiency diseases]]
[[Category:DNA repair and replication disorders]]
[[Category:Rare diseases]]
[[Category:Rare diseases]]
[[Category:Medical terminology]]
{{stub}}
{{Immune disorders}}
{{DNA repair-deficiency disorder}}
{{DEFAULTSORT:Severe Combined Immunodeficiency}}
[[Category:Combined T and B–cell immunodeficiencies]]
[[Category:DNA replication and repair-deficiency disorders]]
[[Category:Genetic disorders by system]]
[[Category:Noninfectious immunodeficiency-related cutaneous conditions]]
[[Category:Noninfectious immunodeficiency-related cutaneous conditions]]
[[Category:Rare diseases]]

Latest revision as of 03:29, 20 March 2025

Genetic disorder causing severe immunodeficiency



Severe Combined Immunodeficiency (SCID)
Microscopic image of immune cells affected by SCID
Synonyms Alymphocytosis, Glanzmann–Riniker syndrome,
Severe mixed immunodeficiency syndrome,
Thymic alymphoplasia
Pronounce
Field Immunology, Pediatrics, Medical genetics
Symptoms Severe, recurrent infections, failure to thrive, chronic diarrhea, pneumonia, oral candidiasis
Complications Life-threatening infections, sepsis, failure to thrive
Onset Infancy
Duration Lifelong (if untreated)
Types X-linked SCID, ADA-SCID, JAK3-SCID, RAG1/RAG2-SCID, IL-7Rα-SCID, etc.
Causes Genetic mutations affecting T-cell and B-cell function
Risks Family history of SCID, consanguinity
Diagnosis Newborn screening (TREC test), lymphocyte count, genetic testing
Differential diagnosis Other primary immunodeficiencies, AIDS, leukemia
Prevention Genetic counseling, prenatal diagnosis
Treatment Bone marrow transplantation, gene therapy, enzyme replacement therapy, prophylactic antibiotics
Medication IVIG, gene therapy, PEG-ADA for ADA-SCID
Prognosis Without treatment: fatal in infancy; with treatment: improved survival
Frequency 1 in 50,000 to 100,000 (X-linked form)
Deaths High without early intervention


David Vetter, famous SCID patient

Severe Combined Immunodeficiency (SCID) is a rare, genetically inherited disorder characterized by profound deficiencies in both T cell and B cell function. It is considered the most severe form of primary immunodeficiency, rendering affected infants highly susceptible to life-threatening infections. The condition results from mutations in genes essential for immune system development, leading to severe immune dysfunction.

SCID is often referred to as the "bubble boy disease" due to the case of David Vetter, who was forced to live in a sterile environment to avoid infections. Without hematopoietic stem cell transplantation (HSCT) or gene therapy, infants with SCID typically die within their first year of life due to severe infections.

Causes and Pathophysiology[edit]

SCID is caused by mutations in various genes involved in lymphocyte development and function. It leads to severe impairments in T-cell, B-cell, and sometimes natural killer (NK) cell function.

Genetic Causes[edit]

There are multiple forms of SCID, each associated with mutations in different genes:

  • X-linked SCID (SCID-X1) – Caused by mutations in the IL2RG gene, leading to absence of T and NK cells but presence of dysfunctional B cells.
  • Adenosine Deaminase Deficiency (ADA-SCID) – Caused by mutations in the ADA gene, leading to toxic metabolite accumulation, which destroys lymphocytes.
  • JAK3 Deficiency – Affects cytokine signaling and prevents normal immune cell development.
  • RAG1/RAG2 Deficiency – Disrupts V(D)J recombination, preventing B and T cell receptor formation.
  • IL-7Rα Deficiency – Prevents T-cell development, leading to T-cell lymphopenia.
  • Other rare forms – Include defects in CD45, ZAP70, and Artemis genes.

All forms of SCID result in absent or dysfunctional T cells, which in turn affects B-cell function, leading to profound immunodeficiency.

Symptoms and Clinical Manifestations[edit]

SCID presents early in infancy with symptoms such as:

  • Severe, recurrent infections (bacterial, viral, fungal)
  • Chronic diarrhea and failure to thrive
  • Oral candidiasis (thrush)
  • Persistent pneumonia, especially due to Pneumocystis jirovecii
  • Skin rashes (may indicate maternal T-cell engraftment)
  • Absent or very small tonsils and lymph nodes

Without intervention, SCID is universally fatal due to overwhelming infections.

Diagnosis[edit]

Early diagnosis of SCID is critical for survival. Newborn screening programs, particularly the T-cell receptor excision circle (TREC) test, have dramatically improved early detection.

Diagnostic Tests

  • Complete blood count (CBC) – Shows low lymphocyte count (<3000 cells/µL).
  • Flow cytometry – Identifies absence or dysfunction of T, B, and NK cells.
  • Genetic testing – Identifies specific mutations causing SCID.
  • Functional immune tests – Assess T-cell proliferation in response to stimuli.

Newborn Screening

  • Many countries have adopted TREC-based screening, which detects low numbers of naïve T cells, allowing early intervention before infections occur.

Treatment[edit]

Without treatment, SCID is fatal. However, several treatment options restore immune function:

1. Hematopoietic Stem Cell Transplantation (HSCT)

  • First-line curative treatment, ideally performed before 3 months of age.
  • Best outcomes occur with matched sibling donors, but alternative donors (haploidentical or unrelated) can be used.

2. Gene Therapy

  • Used in ADA-SCID and X-linked SCID.
  • Involves correcting the patient's own stem cells using viral vectors.
  • Trials show promising long-term immune restoration.

3. Enzyme Replacement Therapy (For ADA-SCID)

  • Pegylated adenosine deaminase (PEG-ADA) provides temporary immune support.
  • Used as a bridge to definitive therapy (HSCT or gene therapy).

4. Supportive Care

  • Immunoglobulin replacement therapy (IVIG) – Prevents infections.
  • Prophylactic antibiotics & antifungals – Reduces infection risk.
  • Strict infection control measures – Isolation and avoidance of live vaccines.

Prognosis[edit]

The prognosis for SCID depends on early diagnosis and treatment:

  • HSCT before 3 months of age – >90% survival rate.
  • Late diagnosis (after severe infections occur) – Poorer outcomes.
  • Untreated SCID – Death within 1–2 years due to infections.

Gene therapy holds long-term curative potential, especially for X-linked SCID and ADA-SCID.

Epidemiology[edit]

  • SCID affects ~1 in 50,000 to 100,000 live births.
  • X-linked SCID is the most common form (~45%).
  • Higher prevalence in consanguineous populations.
  • Newborn screening programs have increased detection rates, leading to earlier treatment and better outcomes.

Notable Cases[edit]

  • David Vetter ("Bubble Boy") – Lived in a sterile plastic enclosure due to SCID, raising awareness about the disease.
  • Ashanti DeSilva – First SCID patient successfully treated with gene therapy.

See Also[edit]

References[edit]

<references/>

External Links[edit]

Immunology
Basics
Immune cells
Immune responses
Immunotherapy
Diagnostic tests
This immunology-related article is a stub.


NIH genetic and rare disease info[edit]

Severe combined immunodeficiency is a rare disease.

Rare and genetic diseases

Rare diseases - Severe combined immunodeficiency

A-Z list of rare diseases
* 0-9 | A - B - C - D - E - F - G - H - I - J - K - L - M - N - O - P - Q - R - S - T - U - V - W - X - Y - Z
Also see
Resources


Metabolic disease: DNA replication and DNA repair-deficiency disorder
DNA replication
DNA repair


This article is a medical stub. You can help WikiMD by expanding it!
PubMed
Wikipedia
Retrieved from "https://wikimd.com/index.php?title=Severe_combined_immunodeficiency&oldid=6531998"