Treatment of infants identified as having severe combined immunodeficiency by means of newborn screening

Abstract

Severe combined immunodeficiency (SCID) is characterized by severely impaired T-cell development and is fatal without treatment. Newborn screening (NBS) for SCID permits identification of affected infants before development of opportunistic infections and other complications. Substantial variation exists between treatment centers with regard to pretransplantation care, and transplantation protocols for NBS identified infants with SCID, as well as infants with other T-lymphopenic disorders detected by using NBS. We developed approaches to management based on the study of infants identified by means of NBS for SCID who received care at the University of California, San Francisco (UCSF). From August 2010 through October 2016, 32 patients with NBS-identified SCID and leaky SCID from California and other states were treated, and 42 patients with NBS-identified non-SCID T-cell lymphopenia were followed. Our center's approach supports successful outcomes; systematic review of our practice provides a framework for diagnosis and management, recognizing that more data will continue to shape best practices.

Keywords: Severe combined immunodeficiency; T cells; T-cell lymphopenia; newborn screening; transplantation.

Conflict of interest statement

Conflict of Interest Statement: The authors have no conflicts of interest relevant to this article to disclose.

Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Identification of T cell immune defects by newborn TREC screening; primary immune defects may also be diagnosed due to a history affected family members or clinical features. *Variable can be Omenn syndrome is a form of leaky SCID with rash; eosinophilia; autoreactive, oligoclonal T cells; and variable CD3 T cell count which can be >1500. ***Some infants never leave this group but some move out of this category when other diagnoses are made. These infants need to be followed over time.

Figure 2

Donor selection and conditioning for typical SCID. 1Excludes Omenn syndrome and leaky SCID, both classified as atypical SCID for transplant purposes and requiring at least some conditioning; also excludes radiation sensitive SCID (DCLREC1, LIG4, etc.), for which donor selection and conditioning are individualized to balance risks of rejection vs. chemotherapy toxicity. 2Gene therapy clinical trials should be considered for X-linked or ADA SCID when there is no HLA matched sibling. 3Based on availability, CMV status, donor age, and other variables. 4Non-radiation-sensitive T-B-NK+ SCID generally requires chemotherapy plus serotherapy for unrelated donor transplant. 5For X-linked and JAK3 SCID a maternal donor with serotherapy alone is preferred over a 9/10 unrelated or 6–7/8 cord donor. 6Consider chemotherapy conditioning for enhanced B and/or T cell reconstitution and to prevent rejection.

Figure 3

Evaluation and management of non-SCID T cell lymphopenia (persistently