Pediatric Severe Combined Immunodeficiency Differential Diagnoses

Updated: Apr 28, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD  more...
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Diagnostic Considerations

Misdiagnosing severe combined immunodeficiency (SCID) as hypogammaglobulinemia is a common error. When patients first present with common bacterial infections such as otitis media and pneumonia, a diagnosis of agammaglobulinemia often is considered. In fact, early descriptions of SCID were termed Swiss agammaglobulinemia.

In almost all cases, flow cytometry immediately distinguishes between B-cell deficiencies and lack of mature T cells. Other immunodeficiency syndromes, particularly DiGeorge syndrome, may lack T-cell function completely and resemble SCID clinically. The nonimmunologic features of these T-cell disorders usually distinguish them.

CD40 ligand (CD154) deficiency—that is, X-linked hypogammaglobulinemia with hyper–immunoglobulin M (IgM)—may present with recurrent otitis media and Pneumocystis pneumonia, as does SCID; the former has normal populations of mature T cells, B cells, and NK cells, unlike most variants of SCID.

In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following:

  • Leiner disease

  • Letterer-Siwe disease

  • Primary immunodeficiency

  • Congenital TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes simplex, or other infections) infection

  • Other forms of hypogammaglobulinemia

Differential Diagnoses