Diagnosis of 22q11.2 Deletion Syndrome and Artemis Deficiency in Two Children with T-B-NK+ Immunodeficiency

Abstract

Two infants are described who presented with 22q11.2 deletion and a T(-)B(-)NK(+) immune phenotype. For both infants, the initial diagnosis was athymia secondary to complete DiGeorge anomaly. The first infant underwent thymus transplantation but 6 months after transplantation had circulating thymus donor T cells; the patient did not develop recipient naïve T cells. Genetic analyses revealed that both patients had Artemis deficiency, a rare form of severe combined immunodeficiency (SCID). Both infants have subsequently undergone bone marrow transplantation. These cases illustrate the importance and paradox of differentiating SCID from complete DiGeorge anomaly because hematopoietic stem cell transplantation (HSCT) is the preferred treatment for SCID but is ineffective for complete DiGeorge anomaly. However, if the thymus is completely absent, donor stem cells from a HSCT would not be able to be educated.

Positive Family History, Infection, Low Absolute Lymphocyte Count (ALC), and Absent Thymic Shadow: Diagnostic Clues for All Molecular Forms of Severe Combined Immunodeficiency (SCID)

“…One Artemis SCID patient who also had DiGeorge syndrome and had a history of a thymus transplant prior to receiving an HLA-haploidentical bone marrow transplant was excluded from the analysis. 20 Absolute lymphocyte counts were calculated from white blood cell counts and manual differentials performed at the time of presentation to this institution. Lymphocyte subpopulation analysis was performed via flow cytometry, and T cell function was assessed by in vitro lymphocyte stimulation studies, as previously described.…”

Defects in Thymic Development

“…128 Likely these children had partial DiGeorge anomaly and SCID due to Artemis deficiency. 128 Likely these children had partial DiGeorge anomaly and SCID due to Artemis deficiency.…”

Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency

“…A retrospective questionnaire-based analysis of 37 children with SCID who had undergone unrelated donor (adult or UCB) transplant without conditioning other than serotherapy was undertaken via a query of all members of the PIDTC and the IEWP-EBMT. Data from some URD 13 and MSD 17, 18 recipients have been previously published. URD HCTs were performed between July 1993 and November 2012 in 8 PIDTC and 8 IEWP-EBMT centers, with a median year of HCT of 2007.…”