Severe Combined Immunodeficiency (SCID)
SCID is inherited in an autosomal recessive or X-linked pattern, depending on the gene.
Normally a person has two functional genes. In people with autosomal recessive SCID, both genes have a mutation that impacts T cell production. Each parent of a newborn with SCID typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
X-linked SCID is caused by a mutation in the IL2RG gene on the X chromosome. Because females have two X chromosomes, they have two IL2RG genes. Because males have one X chromosome, they have one IL2RG gene. Males with a nonfunctioning IL2RG gene have SCID and females with one IL2RG gene mutation will be carriers. When a mother is a carrier of X-linked SCID, each son has a 50% chance of inheriting the disorder.
Carriers of SCID do not have symptoms.
Untreated, essentially all infants with SCID will contract life-threatening infections including bacterial, fungal and viral. Frequent infections can cause poor growth (failure to thrive). With treatment, the immune system becomes functional and infants do not have frequent infections.
- Incidence: The overall incidence of SCID in NYS is approximately 1 in 45,000.
- New York State Method of Screening (First Tier): SCID screening is accomplished by qPCR of T cell receptor excision circles (TRECs), a piece of DNA produced during the formation of T cells in the thymus. Newborns with SCID have little to no TRECs. Although this testing is DNA-based, TREC analysis is not a test for gene mutations.
- Second Tier Screening: None
- Testing can be affected by: TRECs are often lower in premature infants. TRECs may also be low in newborns with congenital birth defects or other syndromes with T cell impairment (DiGeorge syndrome, CHARGE syndrome).
- Interpretation/reporting of data: Results are reported as within acceptable limits, borderline, premature infant or as a referral. A repeat specimen should be collected promptly for a borderline result. For premature infants, a repeat specimen should be collected at 37 weeks gestation. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for SCID are referred to a Specialty Care Center for evaluation by an immunologist or infectious disease specialist trained in the diagnosis and treatment of SCID.
Diagnostic testing includes complete blood count and flow cytometry for T, B and NK cell subsets. Additional testing may include mitogen stimulation, chromosome analysis and genetic testing.
Treatment is dependent on the type of SCID and includes hematopoietic stem cell transplant (HSCT), enzyme replacement therapy and gene therapy. Enzyme replacement therapy is available for one type of SCID (adenosine deaminase deficiency). Prior to transplant, newborns may need to be placed in isolation and receive antibiotics to prevent infection.
Without treatment, the mortality rate is high and the majority of infants will expire before one year of age. The survival rate is at least 94% when infants with SCID are treated by 3.5 months of age.
Severe combined immunodeficiency (SCID) is a group of rare genetic disorders caused by a deficiency or absence of T cells. B cells and/or NK cells may also be low or absent. T cells, B cells and NK cells have an important role in the immune system. Therefore, people with SCID do not have a functioning immune system and are susceptible to infections.
Mutation(s) in one of several genes can cause SCID. In some cases of SCID, a genetic cause is never identified.