IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58 000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

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Athabascan SCID (SCIDA) is an autosomal recessive disorder found among Athabascan-speaking Native Americans and is manifested by the absence of both T and B cells (T−B−NK+ SCID). We previously mapped the SCIDA gene to a 6.5-cM interval on chromosome 10p. SCIDA fibroblasts were found to have defective coding joint and reduced, but precise signal joint formation during V(D)J recombination. After excluding potential candidate genes, we conducted a combined positional candidate and positional cloning approach leading to the identification of nine novel transcripts in the refined SCIDA region. One of the transcripts showed significant homology with the mouse and yeast SNM1/PSO2 and was recently reported (Artemis) to be responsible for another T−B−NK+ SCID condition (radiation sensitive SCID) in 13 patients of primarily European origin. In our evaluation of this gene, we have identified a unique nonsense mutation in 21 SCIDA patients that is closely correlated to the founder haplotypes that we had previously identified. This nonsense founder mutation results in the truncation of the deduced protein product. The wild-type construct of the primary transcript can effectively complement the defective coding joint and reduced signal joint formation in SCIDA fibroblasts. The above results indicate that this SNM1-like gene (Artemis) is the gene responsible for SCIDA. We also discovered three additional alternative exons and detected at least six alternatively spliced SCIDA variants (SCIDA-V1, 2, 3, 4, 5, and 6) coexisting with the primary transcript in trace amounts. Finally, we found that the SCIDA primary transcript (Artemis) encodes a nuclear protein.

OBJECTIVE—To estimate the prevalence and incidence of diabetes, clinical characteristics, and risk factors for chronic complications among Navajo youth, using data collected by the SEARCH for Diabetes in Youth Study (SEARCH study).RESEARCH DESIGN AND METHODS—The SEARCH study identified all prevalent cases of diabetes in 2001 and all incident cases in 2002–2005 among Navajo youth. We estimated denominators with the user population for eligible health care facilities. Youth with diabetes also attended a research visit that included questionnaires, physical examination, blood and urine collection, and extended medical record abstraction.RESULTS—Diabetes is infrequent among Navajo youth aged <10 years. However, both prevalence and incidence of diabetes are high in older youth. Among adolescents aged 15–19 years, 1 in 359 Navajo youth had diabetes in 2001 and 1 in 2,542 developed diabetes annually. The vast majority of diabetes among Navajo youth with diabetes is type 2, although type 1 diabetes is also present, especially among younger children. Navajo youth with either diabetes type were likely to have poor glycemic control, high prevalence of unhealthy behaviors, and evidence of severely depressed mood. Youth with type 2 diabetes had more metabolic factors associated with obesity and insulin resistance (abdominal fat deposition, dyslipidemia, and higher albumin-to-creatinine ratio) than youth with type 1 diabetes.CONCLUSIONS—Our data provide evidence that diabetes is an important health problem for Navajo youth. Targeted efforts aimed at primary prevention of diabetes in Navajo youth and efforts to prevent or delay the development of chronic complications among those with diabetes are warranted.