Clinical Guidance

X-linked severe combined immunodeficiency (X-SCID) comprises a phenotypic spectrum ranging from typical X-SCID (early-onset disease that is fatal if not treated with HSCT) to atypical X-SCID (later-onset disease comprising phenotypes caused by variable immunodeficiency, immune dysregulation, and/or autoimmunity).

Typical X-SCID Clinical Phenotype

Affected males appear normal at birth. However, as the concentrations of transplacentally transferred maternal serum antibodies decline, infants with X-SCID are increasingly prone to infection. Prior to universal newborn screening for SCID, most infants with X-SCID came to medical attention between ages three and six months; presentation with life-threatening infection prior to age three months also occurred.

Source: GeneReviews — "X-Linked Severe Combined Immunodeficiency"

Differential Diagnosis

Since the implementation of newborn screening the incidence of each genetic type of typical severe combined immunodeficiency (SCID) has become clearer. X-SCID has remained one of the most common forms of typical SCID . summarizes genes known to be associated with typical SCID. Table 3. Typical Severe Combined Immunodeficiency: Genetic Causes

Source: GeneReviews — "X-Linked Severe Combined Immunodeficiency"

Clinical Guidance

To ensure the safety of the infant/older individual pending definitive treatment to achieve immunocompetence, parents and other care providers need to avoid the following:

• Breast-feeding and breast milk, until maternal CMV status is established by CMV serologies. CMV is a chronic infection and intermittent viral shedding in various bodily fluids occurs unpredictably. If maternal CMV serology is negative, breast milk may be considered safe for feeding.

Note: Use of pasteurized breast milk while the infant is being prepared for HSCT remains controversial given the severe negative effects of CMV infection in the outcome of HSCT.

• Exposure to young children, sick contacts, or individuals with cold sores in order to decrease the risk of transmission of disease to the infant

• Crowded enclosed spaces due to risk of infectious exposure

• Live viral vaccines for the infant as well as household contacts until after immunocompetence is restored following HSCT

• Transfusion of non-irradiated blood products . Use of leuko-reduced and CMV-negative, irradiated blood products only is recommended.

• Areas of construction or soil manipulation as they increase the risk for fungal exposure

Source: GeneReviews — "X-Linked Severe Combined Immunodeficiency"

Therapies Under Investigation

The following investigations are under way:

Source: GeneReviews — "X-Linked Severe Combined Immunodeficiency"