Severe Combined Immunodeficiency (SCID)

Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

Adenosine Deaminase deficiency
CD3/T cell receptor complex disorders with immunodeficiency
Combined immunodeficiency syndromes
Adenosine Deaminase deficiency
Severe Combined immunodeficiency (SCID) with other defined deficiency (JAK3 or ZAP-70)
Syndromic immunodeficiency
X-linked severe combined immunodeficiency (X-SCID)

ICD-10 Coding

D81.9, Combined immunodeficiency, unspecified

Disorder Category

Immunodeficiency disorder


Abnormal 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
  • Additional testing may be done to confirm the diagnosis and determine the type of SCID, which will determine next steps in management.


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 may be absent or compromised. Impairment of both B and T cells leads to the term “combined.” In certain presentations, NK cells may also be affected in about 50% of patients with SCID. 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.

Clinical Characteristics

Babies with SCID are at high risk for life-threatening infections that can begin as early as 1 month after birth. Most patients are asymptomatic shortly after birth before increasingly severe infections develop.
Without treatment for SCID, individuals suffer from frequent and increasingly severe infections that result in chronic diarrhea, growth faltering, and eventually death within the first 1 or 2 years of life.
With treatment depends on the type of SCID and the cell lines affected. 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] [van: 2019] Infants who receive hematopoietic transplant to reconstitute the immune system prior to 3.5 months of age and before onset of infection have an 80-95% chance of 5-year survival. [Heimall: 2017] 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
  • Recurrent fevers
  • Unexplained lymphopenia
  • Chronic diarrhea
  • Poor weight gain or growth faltering
  • Persistent thrush (candidiasis) in the mouth or throat, mouth ulcers, infections with RSV, HSV, VZV, measles, influenza or parainfluenza viruses
  • Infections from live viral vaccines (rotavirus, MMR, and varicella vaccines)
  • Severe eczematous rash from birth that does not respond to treatment


The incidence of SCID is approximately 1:58,000. [Kwan: 2014]


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

Primary Care Management

Next Steps After a Positive 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).
  • Refer the patient to the pediatric bone marrow transplant (BMT) group.
  • Until testing is complete, avoid exposing the infant to those who are sick and large groups.
  • 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 risk of transfer of CMV from breastmilk. Some treatment centers recommend stopping breastfeeding/breastmilk unless the mother is known to be CMV-negative and will continue to monitor the mother for potential CMV infections when using breastmilk.
  • 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.

Confirming the Diagnosis

  • To confirm the diagnosis of SCID, work with:
  • Patients with positive newborn screening for SCID need to be referred to the Pediatric Bone Marrow Transplant group for further workup and management.
  • Confirmatory testing done by pediatric BMT 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 a 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 genetic variants associated with SCID. Commonly, testing for transplacental maternal engraftment of T cells is performed.

If the Diagnosis is Confirmed

  • After a positive newborn screening test for SCID, the patient will be connected with the pediatric BMT group who will be able to assist the family with management and treatment options and, if needed, discuss hematopoietic stem cell transplant.
  • Educate the family about signs, symptoms, and need for urgent care when the infant becomes ill before being seen by the BMT group.
  • Provide the family with basic information about SCID and T-cell lymphopenia.• Provide the family with basic information about SCID and T-cell lymphopenia.


Information & Support

Related Portal Content
After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.

For Professionals

SCID, X-Linked (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

X-Linked Severe Combined Immunodeficiency (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

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.

For Parents and Patients

X-Linked SCID (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the 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.

Center for Parent Information and Resources (DOE)
Parent Centers in every state provide training to parents of children with disabilities and provide information about special education, transition to adulthood, health care, support groups, local conferences, and other federal, state, and local services. See the "Find Your Parent Center Link" to find the parent center in your state.


ACT Sheet for SCID and Conditions Associated with T Cell Lymphopenia (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 for Patients & Families in Rhode Island (RI)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.


Severe Combined Immunodeficiency (SCID) (
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

Authors & Reviewers

Initial publication: November 2012; last update/revision: June 2024
Current Authors and Reviewers:
Author: Elizabeth Briscoe, MD
Senior Author: Doerthe Adriana Andreae, MD, PhD
Authoring history
2017: update: Karin Chen, MDR
2013: revision: Karin Chen, MDR
2012: first version: Nicole Tattersall, RN BSNA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

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

Heimall J, Puck J, Buckley R, Fleisher TA, Gennery AR, Neven B, Slatter M, Haddad E, Notarangelo LD, Baker KS, Dietz AC, Duncan C, Pulsipher MA, Cowan MJ.
Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immunodeficiency Patients: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT.
Biol Blood Marrow Transplant. 2017;23(3):379-387. PubMed abstract / Full Text

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

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

van der Burg M, Mahlaoui N, Gaspar HB, Pai SY.
Universal Newborn Screening for Severe Combined Immunodeficiency (SCID).
Front Pediatr. 2019;7:373. PubMed abstract / Full Text