17
Figure 2. Diagnosis of Combined or Syndromic
Immunodeficiencies
2.8 Consider other
diagnoses as per
Tables 1 and 6 and text
2.1 Suspected
combined
immunodeficiency or
syndrome; complete
screening of humoral
and cellular immunity
NO
YES
2.2 Clinical
or laboratory
findings consistent
with SCID?
2.6 Manage as
indicated
2.3 T cells
present?
YES
2.4 Investigate
possible
diagnoses
according to
lymphocyte
phenotype as
per Table 7
NO
2.7 T cells of
maternal origin?
NO NO
YES
YES
2.5
Diagnosis
established?
• 2.1– In this situation it is appropriate to perform a complete screening evaluation
of specific immune function, including measurement of immunoglobulin levels,
specific antibody production, enumeration of lymphocyte subpopulations,
measurement of T-cell proliferation with mitogens and antigens, and evaluation of
NK cell cytotoxicity.
• 2.2– Are the clinical presentation and laboratory evaluation consistent with SCID?
Note that in some states SCID might be suspected early on the basis of newborn
screening through measurement of TREC numbers in dried blood spots (see SS
24).
• 2.3– If the answer to 2.2 is yes, consider the T-cell phenotype. Are T cells present?
• 2.4– If the answer to 2.3 is no, this is consistent with SCID, and more specific
diagnostic studies should be undertaken considering the lymphocyte phenotype, as
outlined in Table 5.
• 2.5– Is the diagnosis established?
• 2.6– If the answer to 2.5 is yes, then proceed to manage as indicated (ultimately
HSCT or gene therapy).
• 2.7– If the answer to 2.3 is yes, the origin of the T cells should be determined.
Are the T cells of maternal origin? If the answer to this question is yes, then this is
also consistent with SCID and proceed as in 2.4.
• 2.8– If the T cells are not of maternal origin, then autologous T cells are present,
and the diagnosis is not classic SCID (a diagnosis of leaky SCID is still possible).
Consider and investigate alternative CIDs and syndrome diagnoses as outlined in
Tables 1 and 7 and SSs 26 to 76.
Combined B- and T-Cell Immunodeficiencies
