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).

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...

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 .

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"