Test ID: SNS
Supplemental Newborn Screen, Blood Spot

Presymptomatic identification of disorders to allow for early initiation of treatment and consequent improvement in the long-term prognosis of affected patients.

Early diagnosis may also minimize complications and help avoid unnecessary diagnostic testing and identify families for whom prenatal genetic counseling may be helpful.

Panel includes all disorders recommended by the American College of Medical Genetics (Genet Med 2006;8[Supplement]:1S-11S).

State-mandated newborn screening was initiated in the early 1960s for the identification of infants affected with phenylketonuria (PKU), but soon was expanded to include a few additional genetic and nongenetic conditions. The goal of newborn screening is to detect diagnostic markers of treatable disorders in blood spots collected from presymptomatic newborns on the second day of life.

The early identification of disorders before symptoms manifest is desirable because presymptomatic initiation of treatment can significantly improve the long-term prognosis of affected patients. Inherited disorders of amino acid, fatty acid, and organic acid metabolism typically manifest during the first 2 years of life as acute metabolic crises and usually result in severe neurologic impairment or death. These metabolic decompensations are usually triggered by intermittent febrile illness, such as common viral infections leading to prolonged fasting and increased energy demands. Accordingly, treatment for most of these disorders simply consists of frequent carbohydrate-rich feedings to avoid fasting.

Tandem mass spectrometry (MS/MS) is a powerful multi-analyte screening method that is ideally suited for population-wide testing. Since the early 1990s, MS/MS has made possible the screening for more than 30 genetic disorders affecting the metabolism of amino acids, fatty acids, and organic acids. In our experience, the combined incidence of the disorders identifiable by MS/MS in a single blood spot analysis is approximately 1:1,600 newborns.

A few of the disorders detectable by supplemental newborn screening are not yet treatable satisfactorily. However, the possibility of making the diagnosis early in life not only helps to avoid unnecessary diagnostic testing, but is also beneficial to the patient's families because genetic counseling and prenatal diagnosis can be offered.

The simultaneous MS/MS analysis of amino acids, acylcarnitines, and succinylacetone in dried blood spots can be performed in 3 minutes per specimen, generating metabolite profiles that allow for the biochemical diagnosis of multiple disorders. This is in contrast to conventional screening techniques traditionally based on the principle of 1 separate test for each disorder. The performance of Mayo's supplemental newborn screening program is characterized by a very low false-positive rate of 0.075% and a high positive predictive value of 46%. The positive detection rate is 1 affected case in 1,583 babies screened.

The Biochemical Genetics Laboratory already offers comprehensive diagnostic services for the identification of patients with inborn errors of metabolism by prenatal, high-risk, and postmortem screening. Furthermore, follow-up and confirmatory testing for the disorders detectable by newborn screening can be provided within the Division of Laboratory Genetics in the Department of Laboratory Medicine and Pathology.

See Newborn Screening Follow-up for Isolated C4 Acylcarnitine Elevations; Newborn Screening Follow-up for Elevations of C8, C6, and C10 Acylcarnitine; and Newborn Screening Follow-up for Isolated C5 Acylcarnitines Elevations in Special Instructions for additional information.

See Request for Original Newborn Screening Card in Special Instructions to submit a spot from the original newborn screening card located at your state screening laboratory.

Not applicable

The quantitative measurements of the various amino acids, acylcarnitines, and succinylacetone support the interpretation of the complete profile but for the most part are not diagnostic by themselves. The interpretation is by pattern recognition. Abnormal results are not sufficient to conclusively establish a diagnosis of a particular disease. To verify a preliminary diagnosis, independent biochemical (ie, in vitro enzyme assay) or molecular genetic analyses are required, many of which are offered within the Department of Laboratory Medicine and Pathology Division of Laboratory Genetics.

The reports will be in text form only, values for the more than 60 analytes and analyte ratios will not be provided. A report for a normal screening result will be reported as: "In this blood spot sample, the amino acid and acylcarnitine profiles by tandem mass spectrometry showed no biochemical evidence indicative of an underlying metabolic disorder."

A report for an abnormal screening result will include a quantitative result of the abnormal metabolites, a detailed interpretation of the results, including an overview of the results' significance, possible differential diagnoses, recommendations for additional biochemical testing and confirmatory studies (enzyme assay, molecular analysis), a phone number for one of the contacts at the Mayo Clinic, and a phone number for one of the laboratory directors if the referring physician has additional questions.

See Newborn Screening Follow-up for Isolated C4 Acylcarnitine Elevations; Newborn Screening Follow-up for Elevations of C8, C6, and C10 Acylcarnitine; and Newborn Screening Follow-up for Isolated C5 Acylcarnitines Elevations in Special Instructions for additional information.

Testing is only appropriate for patients <1 week of age as part of prospective newborn screening.

This test is supplemental and not intended to replace state mandated newborn screening.

Test is not appropriate for metabolic screening of symptomatic patients.

In a few instances, falsely abnormal results may occur in the analysis of amino acid and acylcarnitine profiles. To keep the number of false-positive and false-negative results to a minimum, results are interpreted based on the metabolite profiles, the information provided on the newborn screening card, and second tier tests for several nonspecific analytes. Using this approach our false-positive rate is only 0.075%.

Newborns discharged on the first day of life will need to be retested during the first week of life, eg, at the first well-child examination, as is customary for state-mandated newborn screening programs. This is necessary to avoid false-negative amino acid results due to limited protein intake on the first day of life.

Carrier status (heterozygosity) for inborn errors of metabolism cannot be reliably detected by amino acid and acylcarnitine profiling.

The performance of Mayo's supplemental newborn screening program is characterized by a very low false-positive rate of 0.075% (cumulative for 2004-2010; 2010 YTD is 0.036%) and a high positive predictive value of 46% (2010 YTD 65%). The positive detection rate is 1 affected case in 1,583 babies screened (n=505,017).

1. Matern D:Tandem mass spectrometry in newborn screening. Endocrinologist 2002;12:50-57

2. Rinaldo P, Tortorelli S, Matern D:Recent developments and new applications of tandem mass spectrometry in newborn screening. Curr Op Peditr 2004;16:427-433

3. Rinaldo P, Zafari S, Tortorelli S, Matern D:Making the case for objective performing metrics in newborn screening by tandem mass spectrometry. MRDD Res Rev 2006;12:255-261

4. Matern D, Tortorelli S, Oglesbee D, et al:Reduction of the false-positive rate in newborn screening by implementation of MS/MS-based second-tier tests:The Mayo Clinic experience (2004-2007). J Inherit Metab Dis 2007;30(4):585-592

• Request for Original Newborn Screening Card
• Newborn Screening Follow-up for Isolated C4 Acylcarnitine Elevations (also applies to any plasma C4 acylcarnitine elevations)
• Newborn Screening Follow-up for Elevations of C8, C6, and C10 Acylcarnitine (also applies to any plasma C8, C6, and C10 acylcarnitine elevations)
• Newborn Screening Follow-up for Isolated C5 Acylcarnitines Elevations (also applies to any plasma C5 acylcarnitine elevation)