Severe Combined Immunodeficiency (SCID)

Other Names

Adenosine deaminase (ADA) deficiency

Bubble boy disease

XSCID (X-linked recessive form)

Diagnosis Coding

D81.9, combined immunodeficiency, unspecified

Disorder Category

An other newborn disorder

Screening

Finding

Absent or severely reduced T-cell receptor excision circles (TRECs), which are produced during normal T-cell maturation

Tested By

TREC test; PCR-based assay that detects the number of TRECs

Overview

Severe combined immunodeficiency (SCID) includes a group of rare, but serious and potentially fatal inherited immune disorders in which T lymphocytes fail to develop and B lymphocytes either are absent or compromised. Impairment of both B and T cells leads to the term “combined.” Untreated patients develop life-threatening infections. The screening test for TRECs, a byproduct of normal T-cell development, identifies SCID and some related conditions with low T cells that result in less severe immunodeficiency. Some infants with mild to moderately low TRECs have a transient lymphopenic condition related to delay in maturation of the immune system, which can be more common in the neonatal intensive care unit /premature infant population.

Prevalence

Prevalence is approximately 1:58,000. [Kwan: 2014]

Inheritance

There are several types of SCID; the most common form is X-linked recessive, affecting only males, while other forms are autosomal recessive.

Maternal & Family History

About 1/3 of children with SCID may have a family history of infant death due to infection or known SCID. [McWilliams: 2015]

Prenatal Testing

Prenatal testing involves DNA testing or enzyme analysis by amniocentesis or chorionic villus sampling (CVS). It is only recommended if there is a family history of SCID.

Clinical Characteristics

Babies with SCID are at high risk for life-threatening infections that can begin as early as 1 month after birth. Without treatment, individuals suffer from frequent or severe infections that result in rashes, diarrhea, increasing illness, complications, and even death within the first 1 or 2 years of life.

Depending on the type of SCID, treatment modalities include hematopoietic transplant (bone marrow or stem cell), gene therapy (currently an investigational treatment in the United States), or enzyme replacement (for adenosine deaminase deficiency SCID). [Chinn: 2015] Infants who receive hematopoietic transplant to reconstitute the immune system prior to 3.5 months of age have a >95% chance of survival. Transplantation survival decreases to less than 80% after 3.5 months of age, usually because of complications resulting from infections. [Myers: 2002]

Early signs of SCID include:
  • Frequent, severe infections caused by common bacteria, viruses, or opportunistic infections, such as Pneumocystis jirovecii
  • Infections that do not respond appropriately to antibiotic treatment
  • Diarrhea
  • Poor weight gain or growth (failure to thrive)
  • Persistent thrush (candidiasis, a fungal infection) in the mouth or throat
  • Infections from live viral vaccines (rotavirus, MMR, and varicella vaccines)
  • Severe eczematous rash from birth that does not respond to treatment

Follow-up Testing after Positive Screen

Confirmatory testing after an abnormal screening result will include lymphocyte subset enumeration of T, B, and NK cells.

If there are further concerns of SCID or other immune deficiency, full characterization of the immune system will include complete blood count with differential lymphocyte subset enumeration of T, B, and NK cells, antibody levels, lymphocyte proliferation to mitogens, and molecular genetic testing for specific gene diagnosis. In some cases, chimerism studies are completed since some infants with SCID acquire maternal lymphocytes in utero.

Primary Care Management

Upon Notification of the + Screen

  • Contact the family to inform them of the newborn screening result. Point out that additional tests are required to determine whether the baby actually has an immune deficiency (1:10-1:20 of abnormal SCID screening tests in Utah that require confirmatory testing are consistent with SCID. The remainder of abnormal screening tests may include infants with mild-to-moderate immune defects, those with transient delays in T-cell maturation, or those with false positive tests).
  • Until testing is complete, avoid exposing the infant to those who are sick.
  • If the infant has any signs of illness, refer to a pediatric hospital right away for evaluation and potential administration of immune globulin and antibiotics.
  • If the infant requires transfusion of any blood product, be sure that only leukocyte-reduced, irradiated products that are negative for cytomegalovirus (CMV) are used.
  • There is a theoretical risk of transfer of CMV from breastmilk. Some treatment centers recommend stopping breastfeeding/breastmilk unless mother is known to be CMV-negative.
  • DO NOT give live attenuated rotavirus vaccine, which could cause infection and prolonged diarrhea in a baby with SCID. This vaccine is to be given only after an immunology specialist confirms that the baby’s immune system is normal.
  • Consult with a specialist in pediatric immunodeficiency diseases (pediatric allergist/immunologist and/or infectious diseases specialist) who will assist with further testing.
  • Provide the family with basic information about SCID and T-cell lymphopenia. See family resource section, below.

If the Diagnosis is Confirmed

  • Report confirmatory findings to the newborn screening program.
  • Educate the family about signs, symptoms, and the need for urgent care when the infant becomes ill.
  • Consult with a specialist in pediatric immunodeficiency diseases who will be able to assist the family with treatment options and, if needed, a bone marrow transplant.

Specialty Care Collaboration

Initiate consultation and coordinate care with subspecialists who have expertise in pediatric immunodeficiency disease, genetic counseling, and family support services.

Resources

Information & Support

For Professionals

SCID, X-Linked (OMIM)
Extensive review of literature that provides technical information on this genetic disorder; Online Mendelian Inheritance in Man.

X-Linked Severe Combined Immunodeficiency (GeneReviews)
An expert-authored, peer-reviewed, current disease description that applies genetic testing to diagnosis and management information; U.S. National Library of Medicine.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. It includes health supervision guidelines and other useful resources; represents a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

National Newborn Screening & Global Resource Center (NNSGRC)
Fact sheets, data reports, publications, and information for clinicians about genetic screening that includes links to state genetic contacts.

SCID (Immune Deficiency Foundation)
A national organization dedicated to improving the diagnosis, treatment, and quality of life of people with primary immunodeficiency diseases. Comprehensive information for clinicians and families.

Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.

For Parents and Patients

Support

SCID Family Support
Support group and resource guide for families affected by SCID.

SCID: Angels for Life
Information and videos from families sharing their experiences with SCID.

General

X-Linked SCID (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.

SCID - Information for Parents (STAR-G)
A factsheet, written by a genetic counselor and reviewed by genetic specialists, for families who have received an initial diagnosis of a newborn disorder; Screening, Technology, and Research in Genetics.

Baby's First Test: SCID (Genetic Alliance)
Information about early signs, follow-up testing, treatment, accessing care, and expected outcomes. Provides links to support services.

Learning about SCID (National Human Genome Research Institute)
Answers to frequently asked questions about SCID and information about current clinical research.

SCID (Immune Deficiency Foundation)
A national organization dedicated to improving the diagnosis, treatment, and quality of life of people with primary immunodeficiency diseases. Comprehensive information for clinicians and families.

Newborn Screening Information for Families (NNSGRC)
Information for families about genetic screening. Links to support groups, advocacy groups, and state genetic contacts; National Newborn Screening and Global Resource Center.

Center for Parent Information and Resources (DOE)
A large resource library related to children with disabilities. Parent Centers in every state provide training to parents of children with disabilities and provide information about local conferences, support groups, and finding schools and other local services; Department of Education, Office of Special Education.

Patient Education

SCID (Immune Deficiency Foundation)
A national organization dedicated to improving the diagnosis, treatment, and quality of life of people with primary immunodeficiency diseases. Comprehensive information for clinicians and families.

Tools

ACT Sheet for SCID (ACMG) (PDF Document 279 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Services

Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

We currently have no Newborn Screening Programs service providers listed; search our Services database for related services.

Pediatric Genetics

We currently have no Pediatric Genetics service providers listed; search our Services database for related services.

Pediatric Hematology/Oncology

See all Pediatric Hematology/Oncology services providers (14) in our database.

Pediatric Immunology/Rheumatology

See all Pediatric Immunology/Rheumatology services providers (1) in our database.

Pediatric Infectious Disease

See all Pediatric Infectious Disease services providers (6) in our database.

For other services related to this condition, browse our Services categories or search our database.

Authors

Author: Nicole Tattersall, RN BSN - 11/2012
Reviewing Authors: Karin Chen, MD - 2/2017
Content Last Updated: 2/2017

Page Bibliography

Chinn IK, Shearer WT.
Severe Combined Immunodeficiency Disorders.
Immunol Allergy Clin North Am. 2015;35(4):671-94. PubMed abstract

Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, et al.
Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States.
JAMA. 2014;312(7):729-38. PubMed abstract / Full Text

McWilliams LM, Dell Railey M, Buckley RH.
Positive Family History, Infection, Low Absolute Lymphocyte Count (ALC), and Absent Thymic Shadow: Diagnostic Clues for All Molecular Forms of Severe Combined Immunodeficiency (SCID).
J Allergy Clin Immunol Pract. 2015;3(4):585-91. PubMed abstract / Full Text

Myers LA, Patel DD, Puck JM, Buckley RH.
Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival.
Blood. 2002;99(3):872-8. PubMed abstract