Clinical Guidance

Typical X-SCID clinical phenotype is usually associated with functionally null IL2RG pathogenic variants resulting in the T–B+NK– immunophenotype. Atypical X-SCID clinical phenotype. Males with hypomorphic IL2RG variants that result in either production of a small amount of gene product or a protein with residual activity may have an atypical disease characterized as T+B+NK– or even nearly normal T and NK cells depending on the functionality of the variant [, , , , , , ]. One exception is the IL2RG variant . All reported individuals with this variant have had opportunistic infections within the first year of life, despite the presence of nearly normal numbers of T cells and NK cells .

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

Diagnostic Criteria

The Primary Immune Deficiency Treatment Consortium (PIDTC) has established laboratory-based definitions for SCID . Infants with typical SCID have 300 autologous T cells per L, absent nave T cells, and poor proliferative responses to the mitogen phytohemagglutinin (10% of control values). Engraftment of maternal cells needs to be tested and excluded. Infants can also have hypomorphic SCID-related gene variants that allow residual function and produce an atypical phenotype (also known as "leaky" SCID) often with 1500 T cells per L.

Suggestive Findings

There are two scenarios in which X-SCID may be considered: an abnormal SCID newborn screening and a symptomatic male with suggestive findings. Both scenarios warrant immediate subspecialty immunologic evaluation and steps taken to ensure the safe...

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

Management Guidelines

Management is discussed in three subsections: issues relating to , those relating to , and those for .

Typical X-SCID Clinical Phenotype

Clinical practices and protocols for typical X-linked severe combined immunodeficiency (X-SCID) can vary depending on the center; however, many aspects overlap in an effort to minimize infection and maximize pre-hematopoietic stem cell transplantation (HSCT) management in infants with abnormal newborn screening results. The following outlines management based on the Primary Immune Deficiency Treatment Consortium (PIDTC) analysis .

Evaluations Following Initial Diagnosis

The following evaluations are indicated:

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"

Surveillance Guidelines

After successful HSCT, routine evaluation of affected males every six to 12 months is indicated to monitor lineage specific donor cell engraftment, growth, immune and lung function, and gastrointestinal and dermatologic issues. If conditioning chemotherapy was used, long-term monitoring of vital organ function and neurodevelopmental progress is also warranted.

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