Severe combined immune deficiency (SCID)

Alternative names	“Bubble baby” disease Primary immune deficiencies Severe T-Cell lymphopaenia
About the condition	SCID is the most severe form of primary or inherited immune deficiency. It results in low or absent T lymphocytes and is due to genetic defects, which cause interruption to the development and maturation of T lymphocytes. Some forms of SCID can also affect the development of B lymphocytes and NK lymphocytes. Lymphocytes are important cells of the immune system responsible for fighting infections. Without them, babies can quickly become overwhelmed by severe bacterial, viral or fungal infections.
Inheritance	The most common form of SCID is X-linked and the remainder are autosomal recessive.
Year started screening in WA	2023
Incidence in WA	1:50,000 (estimated in WA)
Defect	Multiple genetic defects have been identified. All lead to failure to produce functional T lymphocytes or increased destruction of T cells due to accumulation of toxic metabolites. Some conditions may also affect NK and B lymphocyte development.
Symptoms if untreated	Infants with SCID appear well at birth but can quickly develop overwhelming infection as they are unable to clear pathogens. They present with: Recurrent and or severe infection Opportunistic infections eg. Pneumocystis jirovecii Growth faltering Chronic gastrointestinal losses Some forms of SCID may present with severe early onset eczema SCID is usually fatal by 12-18 months if left untreated
Determinants on bloodspot screening	Reduced numbers of T-cell Receptor Excision circles (TRECs) which are a bi-product of T cell development. SCID newborn screening will also measure KRECs – Kappa-deleting Recombination excision circles which are a bi-product of B cell development.
Diagnostic tests	Immunoglobulins Lymphocyte subsets including naïve T cells Confirmatory testing via genetic sequencing is used to identify the specific gene defect which will direct therapy decisions
Treatment	Immediate treatment includes antimicrobial therapies to prevent infection (antibiotics, antiviral and antifungal medications). Definitive treatment usually requires a bone marrow or stem cell transplant but in some instances the defect can also be treated with gene therapy or thymic transplant (less common).
Screening issues	Preterm babies, unwell babies or babies whose mothers are on immunosuppression medications may have transiently low T lymphocytes at birth which spontaneously resolve. There are other more common conditions resulting in low T cell levels. These patients may also be detected by SCID NBS methods.