OBJECTIVES: Newborn screening for severe combined immunodeficiency (SCID) was instituted in California in 2010. In the ensuing 6.5 years, 3 252 156 infants in the state had DNA from dried blood spots assayed for T-cell receptor excision circles (TRECs). Abnormal TREC results were followed-up with liquid blood testing for T-cell abnormalities. We report the performance of the SCID screening program and the outcomes of infants who were identified.METHODS: Data that were reviewed and analyzed included demographics, nursery summaries, TREC and lymphocyte flow-cytometry values, and available follow-up, including clinical and genetic diagnoses, treatments, and outcomes.RESULTS: Infants with clinically significant T-cell lymphopenia (TCL) were successfully identified at a rate of 1 in 15 300 births. Of these, 50 cases of SCID, or 1 in 65 000 births (95% confidence interval 1 in 51 000-1 in 90 000) were found. Prompt treatment led to 94% survival. Infants with non-SCID TCL were also identified, diagnosed and managed, including 4 with complete DiGeorge syndrome who received thymus transplants. Although no cases of typical SCID are known to have been missed, 2 infants with delayed-onset leaky SCID had normal neonatal TREC screens but came to clinical attention at 7 and 23 months of age.CONCLUSIONS: Population-based TREC testing, although unable to detect immune defects in which T cells are present at birth, is effective for identifying SCID and clinically important TCL with high sensitivity and specificity. The experience in California supports the rapid, widespread adoption of SCID newborn screening.

, on behalf of the California Cystic Fibrosis Newborn Screening Consortium abstract OBJECTIVES: This article describes the methods used and the program performance results for the first 5 years of newborn screening for cystic fibrosis (CF) in California.METHODS: From July 16, 2007, to June 30, 2012, a total of 2 573 293 newborns were screened for CF by using a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens; (2) testing 28 to 40 selected cystic fibrosis transmembrane conductance regulator (CFTR) mutations in specimens with immunoreactive trypsinogen values $62 ng/mL (top 1.6%); and (3) performing DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with $2 mutations/variants were referred to CF care centers for diagnostic evaluation and follow-up. Infants with 1 mutation were considered carriers and their parents offered telephone genetic counseling.RESULTS: Overall, 345 CF cases, 533 CFTR-related metabolic syndrome cases, and 1617 carriers were detected; 28 cases of CF were missed. Of the 345 CF cases, 20 (5.8%) infants were initially assessed as having CFTR-related metabolic syndrome, and their CF diagnosis occurred after age 6 months (median follow-up: 4.5 years). Program sensitivity was 92%, and the positive predictive value was 34%. CF prevalence was 1 in 6899 births. A total of 303 CFTR mutations were identified, including 78 novel variants. The median age at referral to a CF care center was 34 days (18 and 37 days for step 2 and 3 screening test-positive infants, respectively). CONCLUSIONS:The 3-step model had high detection and low false-positive levels in this diverse population. WHAT'S KNOWN ON THIS SUBJECT:Several newborn screening models for cystic fibrosis (CF) exist, including DNA-based models that use mutation panels. There is limited experience with models (such as used in California) that include comprehensive DNA sequence testing methods as part of newborn screening.WHAT THIS STUDY ADDS: California' s 3-step newborn screening model for CF showed high efficiency, sensitivity, and positive predictive value. More than 300 mutations were found, reflecting the state' s diverse population. Some CF transmembrane conductance regulator-related metabolic syndrome cases converted to CF over time.

ORIGINAL RESEARCH ARTICLEPurpose: The purpose of this study was to describe the birth prevalence of genetic disorders among different racial/ethnic groups through population-based newborn screening data. methods: Between 7 July 2005 and 6 July 2010 newborns in California were screened for selected metabolic, endocrine, hemoglobin, and cystic fibrosis disorders using a blood sample collected via heel stick. The race and ethnicity of each newborn was self-reported by the mother at the time of specimen collection.Results: Of 2,282,138 newborns screened, the overall disorder detection rate was 1 in 500 births. The disorder with the highest prevalence among all groups was primary congenital hypothyroidism (1 in 1,706 births). Birth prevalence for specific disorders varied widely among different racial/ethnic groups. conclusion:The California newborn screening data offer a unique opportunity to explore the birth prevalence of many genetic dis orders across a wide spectrum of racial/ethnicity classifications. The data demonstrate that racial/ethnic subgroups of the California newborn population have very different patterns of heritable disease expression. Determining the birth prevalence of these disorders in California is a first step to understanding the short-and long-term medical and treatment needs faced by affected communities, especially those groups that are impacted by more severe disorders. 2012:14(11):937-945 Genet Med

Objective. Population-based surveillance data from California and Georgia for years 2004 through 2008 were linked to state death record files to determine the all-cause death rate among 12,143 patients identified with sickle cell disease (SCD).Methods. All-cause death rates, by age, among these SCD patients were compared with all-cause death rates among both African Americans and the total population in the two states. All-cause death rates were also compared with death rates for SCD derived from publicly available death records: the compressed mortality files and multiple cause of death files.Results. Of 12,143 patients identified with SCD, 615 patients died. The all-cause mortality rate for the SCD population was lower than the all-cause mortality rate among African Americans and similar to the total population all-cause mortality rates from birth through age 4 years, but the rate was higher among those with SCD than both the African American and total population rates from ages 5 through 74 years. The count of deceased patients identified by using population-based surveillance data (n5615) was more than twice as high as the count identified in compressed mortality files using SCD as the underlying cause of death alone (n5297).Conclusion. Accurate assessment of all-cause mortality and age at death requires long-term surveillance via population-based registries of patients with accurately diagnosed SCD.