SNS/82594 Overview: Supplemental Newborn Screen, Blood Spot

Test Catalog

Test Name

Normal View

Test ID: SNS
Supplemental Newborn Screen, Blood Spot

Useful For Suggests clinical disorders or settings where the test may be helpful

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

 

The conditions identifiable by amino acid and acylcarnitine analysis are detected by supplemental newborn screening using tandem mass spectrometry (MS/MS) as described here.

 

Analyte

(assay platform)

ACMG Recommended Conditions

Additional Conditions/Treatment Detectable by MS/MS

Core Condition

Secondary Targets

Amino Acids (MS/MS)

Phe

PKU

BS

HPA

REG

TPN

Leu/Ile, Val

MSUD

 

TPN

Met

HCY

Met

TPN, nonspecific liver disease

Cit, Arg, ASA

ASA

CIT

ARG

CIT-II

 

Tyr

TYR-I

TYR-II

TYR-III

Nonspecific liver disease

GUAC

 

 

GAMT

Acylcarnitines (MS/MS)

C0

CUD

 

Maternal CUD, maternal GA-I, maternal MCAD

C3

CblA, Cbl B

MUT

PA

Cbl C, Cbl D

 

C4

 

IBDH

SCAD

FIGLU

C5

IVA

SBCAD

Antibiotics containing pivalic acid

C5-OH

BKT

HMG

MCC

MCD

MGA-I

MHBD

Maternal MCC,

biotinidase deficiency

C8

MCAD1

GA-II1

MCKAT1

M/SCHAD1

 

C3-DC

 

MAL

 

C10:2

 

DR

 

C5-DC

GA-I

 

 

C14:1, C16, C18:1

VLCAD

CACT

CPT-I2

CPT-II

 

C16-OH

LCHAD2

TFP2

 

 

m/z 225<399<473

 

 

Dextrose infusion

m/z 342 (C8:1)

 

 

Artifact often observed in premature neonates

m/z 470 (C16:1OH)

 

 

Cefotaxime metabolite

Succinylacetone

TYR-I

 

 

Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request

Panel includes all disorders recommended by the American College of Medical Genetics detectable by Tandem Mass Spectrometry.(MS/MS)(1)

Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.

See Informative Markers for Supplemental Newborn Screening at Mayo Clinic in Special Instructions.

 

The following algorithms are available in Special Instructions:

-Newborn Screening Follow-up for Elevations of C8, C6, and C10 Acylcarnitines (also applies to any plasma C8, C6, and C10 acylcarnitine elevations)

-Newborn Screening Follow-up for Isolated C4 Acylcarnitine Elevations (also applies to any plasma C4 acylcarnitine elevation)

-Newborn Screening Follow-up for Isolated C5 Acylcarnitine Elevations (also applies to any plasma C5 acylcarnitine elevation)

Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test

Method Name A short description of the method used to perform the test

Flow Injection Analysis-Tandem Mass Spectrometry (MS/MS)

NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.

Conditional

Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name

Supplemental Newborn Screen, BS

Aliases Lists additional common names for a test, as an aid in searching

Blood Spots
Expanded Newborn Screen, Blood Spot
Newborn Screen
Newborn Screening
Newborn Supplemental Screen, Blood Spot

Specimen Type Describes the specimen type needed for testing

Whole blood

Additional Testing Requirements

A repeat specimen is required within 1 week of birth for infants tested before they are 12 hours old.

Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.

Patient must be older than 12 hours and less than 1 week of age.

 

Supplies: Card-Blood Spot Collection Filter Paper (T493)

Preferred: Blood Spot Collection Card (T493)

Acceptable: Whatman Protein Saver 903 Paper, Ahlstrom 226 filter paper

Specimen Volume: 3 Blood spots

Collection Instructions:

1. Do not use device or capillary tube containing EDTA to collect specimen.

2. Do not expose specimen to heat or direct sunlight.

3. Do not stack wet specimens.

4. Keep specimen dry.

5. If collection of a new specimen is necessary, let blood dry on the Blood Spot Collection Card (T493) at ambient temperature in a horizontal position for 3 hours.

Additional Information: For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.

Blood Spots: 1

Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected

Hemolysis

NA

Lipemia

NA

Icterus

NA

Other

Blood spot specimen that shows serum rings or has multiple layers

Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.

Specimen TypeTemperatureTime
Whole bloodAmbient (preferred)
 Frozen 
 Refrigerated 

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Newborn screening as a public health measure was initiated in the early 1960s for the identification of infants affected with phenylketonuria (PKU). Since then, additional genetic and nongenetic conditions were included in state screening programs. The goal of newborn screening is to detect diagnostic markers of the selected disorders in blood spots collected from presymptomatic newborns. 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. Early identification of affected newborns allows for early initiation of treatment to avoid mortality, morbidity, and disabilities due to these disorders.

 

Tandem mass spectrometry (MS/MS) is a powerful multianalyte screening method, which is ideally suited for population-wide testing. Since the early 1990s, MS/MS has made screening possible for more than 30 genetic disorders affecting the metabolism of amino acids, fatty acids, and organic acids based on the profiling of amino acids and acylcarnitines in blood spots. The simultaneous MS/MS analysis of amino acids, acylcarnitines, and succinylacetone in dried blood spots can be performed in less than 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. In Mayo's experience, the combined incidence of the disorders identifiable by MS/MS in a single blood spot analysis is approximately 1 in 1,700 newborns.

 

Supplemental newborn screening by MS/MS as described here does not replace current state screening programs, because MS/MS does not allow primary screening for galactosemia, congenital hypothyroidism, congenital adrenal hyperplasia (CAH), cystic fibrosis, biotinidase, sickle cell disease, Mucopolysaccharidosis type II, Adrenoleukodystrophy, Pompe disease, severe combined immune deficiency (SCID), critical congenital heart disease, and congenital hearing loss.

 

The Secretary's Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC) recommends all programs screen for 34 core disorders (available at http://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/recommendedpanel/).

These conditions are considered to fulfill 3 basic principles:

-Condition is identifiable at a period of time (24-48 hours after birth) at which it would not ordinarily be clinically detected.

-Test with appropriate sensitivity and specificity is available.

-Demonstrated benefits of early detection, timely intervention, and efficacious treatment.

*This test does not screen for critical congenital heart disease and congenital hearing loss, both of which are tested in the nursery using methods other than blood spots (audiometry, pulse oximetry).

 

Screening tests do not conclusively determine disease status, but measure analytes which in most cases are not specific for a particular disease. This is the reason why the HHS Secretary also recognizes more than 25 additional conditions as secondary targets that do not meet all inclusion criteria but are identified nevertheless because most of them are components of the differential diagnosis of screening results observed in core conditions. Even for the secondary conditions, the possibility of making a diagnosis early in life not only helps avoid unnecessary diagnostic testing, but is also beneficial to the patient's families because genetic counseling and prenatal diagnosis can be offered.

 

Although not currently in the recommended uniform screening panel, guanidinoacetate methyltransferase (GAMT), a disorder of creatine synthesis, is a condition included in the Mayo Medical Laboratories' supplemental newborn screen. When untreated, this disorder results in a depletion of cerebral creatine leading to global developmental delays, intellectual disability, severe speech delays, and seizures. Patients with GAMT exhibit behavioral problems and features of autism. Treatment consists of lifelong supplementation with creatine monohydrate, ornithine, and dietary protein restriction to decrease cerebral GAA levels. Individuals with GAMT who are treated before the appearance of symptoms may exhibit normal neurodevelopmental outcomes.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report is provided

Interpretation Provides information to assist in interpretation of the test results

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 Mayo Clinic's Division of Laboratory Genetics.

 

The reports are in text form only, values for the more than 60 analytes and analyte ratios are not provided. A report for a normal screening result is 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 includes 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), and a phone number for a contact at Mayo Clinic if the referring physician has additional questions.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Testing is only appropriate for patients less than 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. In 2013, testing of 71,207 newborns lead to the referral of 55 cases, 38 of them were later confirmed as true positives. These data correspond to a false positive rate of 0.024% and a positive predictive value of 69%.

 

Newborns discharged before 12 hours 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.

Supportive Data

The performance of Mayo's supplemental newborn screening program is characterized by a very low false-positive rate of 0.024% and a high-positive predictive value of 69%. The positive detection rate is 1 affected case in 1,735 babies screened (n=742,449).

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Watson MS, Mann MY, Lloyd-Puryear MA, et al: Newborn Screening: toward a uniform screening panel and system. Genet Med 2006;8(5):1S-11S

2. 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

3. 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

4. McHugh D, Cameron CA, Abdenur JE, et al: Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project. Genet Med 2011;13:230-254

5. Marquardt G, Currier R, McHugh DM, et al: Enhanced interpretation of newborn screening results without analyte cutoff values. Genet Med 2012;14:648-655

6. Hall PL, Marquardt G, McHugh DMS, et al: Post-analytical tools improve performance of newborn screening by tandem mass spectrometry. Genet Med 2014;16:889-895

7. Turgeon C, Magera MJ, Allard P, et al: Combined newborn screening for succinylacetone, amino acids, and acylcarnitines in dried blood spots. Clin Chem 2008;54:657-664

Method Description Describes how the test is performed and provides a method-specific reference

In the United States, every newborn undergoes state-mandated screening on the second day of life or before leaving the hospital. Blood from a heel prick is dripped onto a filter paper card. The blood is left to dry before sending the filter paper card along with pertinent demographic information to the screening laboratory.

 

Blood for the supplemental newborn screening is collected in the same way and then sent to the Biochemical Genetics Laboratory, after obtaining parental consent. A 1/8-inch (3-mm) disk is punched out of the blood spot onto 96-well plate. Then, the amino acids and acylcarnitines are extracted by the addition of methanol and known concentrations of isotopically labeled amino acids and acylcarnitines as internal standards. The extract is moved to another 96-well plate, dried under a stream of nitrogen, and derivatized by the addition of n-butanol hydrochloric acid. In a parallel process, succinylacetone is extracted from the residual blood spot, derivatized with an acidic hydrazine solution, evaporated and combined with the amino acid and acylcarnitine extract amino acids and acylcarnitines are measured as their butyl esters with the hydrazone derivative of succinylacetone by electrospray tandem mass spectrometry (MS/MS). The concentrations of the analytes are established by computerized comparison of ion intensities of these analytes to that of the respective internal standards.(Turgeon C, Magera MJ, Allard P, et al: Combined newborn screening for succinylacetone, amino acids, and acylcarnitines in dried blood spots. Clin Chem 2008;54:657-664)

PDF Report Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.

Monday through Saturday; 9 a.m.

Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.

2 days

Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result

3 days

Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Indefinitely

Performing Laboratory Location The location of the laboratory that performs the test

Rochester

Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.

The test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S Food and Drug Administration.

CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83789

LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and result codes of this test.

LOINC codes are provided by the performing laboratory.

Test IDTest Order NameOrder LOINC Value
SNSSupplemental Newborn Screen, BS54089-8

 

Result IDTest Result NameResult LOINC Value
82594Supplemental Newborn Screen Result54089-8
23727Reviewed By59462-2