Comparative evaluation of newborn bloodspot specimen cards by experienced laboratory personnel and by an optical scanning instrument.

A major factor in determining the suitability of a dried blood spot (DBS) specimen is the subjective nature of evaluation by laboratory personnel. Using newborn screening DBS specimen cards as they were submitted to a public health NBS program, we conducted a systematic pilot study of DBS evaluation by multiple experienced laboratory personnel (ELP) and by an automated optical scanning instrument (OSI) (CardScan (tm), BSD Robotics). OSI confirmed the satisfactory status of all newborn DBS specimen cards that passed initial review by the first ELP. Among the questionable cards selected for further review, 58% passed multiple ELP consensus assessment, and 62% passed OSI evaluation. The overall agreement between ELP and OSI was 86%. Among questionable specimen cards, ELP and OSI were more strongly correlated when multiple ELP assessment was unanimous. We conclude that subjective assessment by ELP is essential and that OSI evaluation is a useful adjunct when ELP assessment does not reach consensus. OSI further allows the selection of optimal locations for punching DBS from unsatisfactory or questionable specimens, optimizing the quality of interim analyses that may be conducted while repeat specimens are being collected. Instrument evaluation of specimen cards would also be valuable as an independent reference method for training laboratory and specimen collection personnel. OSI technology merits further studies to confirm and extend our findings.

Newborn screening for spinal muscular atrophy: Anticipating an imminent need.

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. Children with type I SMA typically die by the age of 2 years. Recent progress in gene modification and other innovative therapies suggest that improved outcomes may soon be forthcoming. In animal models, therapeutic intervention initiated before the loss of motor neurons alters SMA phenotype and increases lifespan. Presently, supportive care including respiratory, nutritional, physiatry, and orthopedic management can ameliorate clinical symptoms and improve survival rates if SMA is diagnosed early in life. Newborn screening could help optimize these potential benefits. A recent report demonstrated that SMA detection can be multiplexed at minimal additional cost with the assay for severe combined immunodeficiency, already implemented by many newborn screening programs. The public health community should remain alert to the rapidly changing developments in early detection and treatment of SMA.

Outcomes from tandem mass spectrometry (MS/MS) workshops in the United States and the performance evaluation of MS/MS laboratories.

Disorders of fatty acid oxidation and organic acid metabolism produce serious clinical problems including death. Introduction of MS/MS technology for newborn screening allowed detection of these disorders in a single process, more than doubling the number of disorders that can be detected from dried-blood spots in newborn screening. Expanded newborn screening has become a critical issue with increased public awareness and demands. Screening by MS/MS is operational in several private testing and public health laboratories. Guidelines and quality assurance services are essential to enhance program expansions. The first of two workshops was organized in June 2000 and the second in September of 2001 to discuss procedures for integrating MS/MS into newborn screening programs. Both workshops addressed technical problems encountered with implementing MS/MS testing. One outcome of the first workshop was a pilot survey for assessing performance of MS/MS laboratories worldwide, which occurred in September 2000. This pilot survey led to the expansion of the proficiency testing services to include MS/MS testing. There are 32 participating laboratories, three of the ten countries represented are from the Asia-Pacific Region.

Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review.

Severe combined immunodeficiency (SCID) is an inherited immune disorder characterized by T-cell lymphopenia (TCLP), a profound lack of cellular (T-cell) and humoral (B-cell) immunity and, in some cases, decreased NK-cell number and function. Affected children develop severe bacterial and viral infections within the first 6 months of life and die before 1 year of age without treatment. Mutations in any of eight known genes: IL2RG, ARTEMIS, RAG1, RAG2, ADA, CD45, JAK3, and IL7R cause SCID. Mutations in unidentified genes may also cause SCID. Population-based genotype and allelic frequencies of these gene defects have not been measured. Some minimal estimates of SCID prevalence are presented. Currently, hematopoietic stem cell transplants are the standard treatment. In clinical trials, gene therapy has been used to reconstitute immune function in patients with IL2RG and ADA defects. The availability of effective therapies, plus the short asymptomatic period after birth, (when stem-cell transplantation is most effective), make SCID a potentially good candidate for newborn screening. Dried blood spots are currently collected from all infants at birth for newborn metabolic screening. Tests for TCLP on dried blood spots could be developed as a screen for SCID. Because SCID may be unrecognized, with infant deaths from infection attributed to other causes, newborn screening is the only way to ascertain true birth prevalence. Validated tests and pilot population studies are necessary to determine newborn screening's potential for identifying infants with SCID.

DNA banking for epidemiologic studies: a review of current practices.

To study genetic risk factors for common diseases, researchers have begun collecting DNA specimens in large epidemiologic studies and surveys. However, little information is available to guide researchers in selecting the most appropriate specimens. In an effort to gather the best information for the selection of specimens for these studies, we convened a meeting of scientists engaged in DNA banking for large epidemiologic studies. In this discussion, we review the information presented at that meeting in the context of recent published information. Factors to be considered in choosing the appropriate specimens for epidemiologic studies include quality and quantity of DNA, convenience of collection and storage, cost, and ability to accommodate future needs for genotyping. We focus on four types of specimens that are stored in these banks: (1) whole blood preserved as dried blood spots; (2) whole blood from which genomic DNA is isolated, (3) immortalized lymphocytes from whole blood or separated lymphocytes, prepared immediately or subsequent to cryopreservation; and (4) buccal epithelial cells. Each of the specimens discussed is useful for epidemiologic studies according to specific needs, which we enumerate in our conclusions.