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Test ID: SNS Supplemental Newborn Screen, Blood Spot

Reporting Name

Supplemental Newborn Screen, BS

Useful For

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

 

 

Testing Algorithm

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)

Specimen Type

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


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

Blood Spots: 1

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Ambient (preferred)
  Frozen 
  Refrigerated 

Reference Values

An interpretive report is provided

Day(s) and Time(s) Performed

Monday through Saturday; 9 a.m.

Test Classification

This test was developed and its performance characteristics 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

83789

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SNS Supplemental Newborn Screen, BS 54089-8

 

Result ID Test Result Name Result LOINC Value
82594 Supplemental Newborn Screen Result 54089-8
23727 Reviewed By 59462-2

Clinical Information

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.

Interpretation

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.

Clinical Reference

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

Analytic Time

2 days

Method Name

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

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical