Invitae Metabolic Disorders Newborn Screening Confirmation Panel

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  • Test code: 06102
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Test description

The Invitae Metabolic Disorders Newborn Screening Confirmation Panel analyzes 64 genes associated with metabolic conditions present in most United States newborn screening (NBS) programs. This panel may be appropriate for symptomatic infants, premature infants or babies in the neonatal intensive care unit where confounding factors, such as liver immaturity or total parenteral nutrition, cause an increased chance of ambiguous screening results on traditional, biochemical-based testing. This panel is not appropriate for screening healthy, asymptomatic newborns. Genetic testing of these genes may confirm a suspected diagnosis and help guide treatment and management decisions.

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Primary panel (64 genes)

ACAD8 ACADM ACADS ACADSB ACADVL ACAT1 ALDH4A1 ARG1 ASL ASS1 AUH BCKDHA BCKDHB BTD CBS CFTR CPS1 CPT1A CPT2 DBT ETFA ETFB ETFDH ETHE1 FAH FTCD G6PD GAA GALE GALK1 GALT GCDH GCH1 GLA HADH HADHA HADHB HLCS HMGCL HSD17B10 IVD MAT1A MCCC1 MCCC2 MLYCD MMAA MMAB MMACHC MMADHC MTRR MUT OAT OTC PAH PCBD1 PCCA PCCB PRODH PTS QDPR SLC22A5 SLC25A13 SLC25A20 TAZ

CFTR: Analysis includes the intronic variants: NM_000492.3:c.3718-2477C>T (also known as 3849+10kbC>T), c.1210-34TG[12]T[5] (also known as T5TG12), c.1210-34TG[11]T[5] (also known as T5TG11), and c.1679+1634A>G.
GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.
GALT: Analysis includes the 5 kb deletion NM_000155.3:c.[-1039_753del; 820+50_*789delinsGAATAGACCCCA] as well as the Duarte variant NM_000155.3: c.-119_-116delGTCA.
GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
MTRR: Analysis includes the intronic variant NM_002454.2:c.903+469T>C.

Add-on preliminary-evidence gene (1 gene)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. DECR1, a gene that has preliminary evidence of association with 2,4-Dienoyl-CoA reductase deficiency can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

DECR1

Add-on generalized leukodystrophies genes (5 genes)

Clinicians can choose to include 5 disorders (metachromatic leukodystrophy, Canavan disease, Krabbe disease, Tay Sachs disease, and Sandhoff disease) that can cause leukodystrophy at an early age as part of this panel. Krabbe disease is currently included in newborn screening in the state of New York; however, since the implementation of this disorder, its inclusion has remained controversial. These genes can be added at no additional charge.

ARSA ASPA GALC HEXA HEXB

GALC: Analysis includes the large (30 kb) deletion for Krabbe Disease.

Add-on congenital disorders of glycosylation genes (36 genes)

Clinicians can choose to include genes associated with congenital disorders of glycosylation. Many of these disorders can present in the newborn period with findings such as hypotonia, seizures, brain imaging abnormalities, hepatopathy, coagulopathy, microcephaly, as well as others. These genes may be included at no extra charge.

ALG1 ALG11 ALG12 ALG13 ALG2 ALG3 ALG6 ALG8 ALG9 ATP6V0A2 B3GLCT CHST14 COG1 COG4 COG5 COG6 COG7 COG8 DOLK DPAGT1 DPM1 DPM2 DPM3 MGAT2 MOGS MPDU1 MPI NGLY1 PGM1 PMM2 RFT1 SLC35A1 SLC35A2 SLC35C1 SRD5A3 TMEM165

Add-on creatine transporter deficiency gene (1 gene)

For some disorders, newborn screening is not currently possible due to lack of a specific analyte that is cost-effective for NBS labs. With molecular testing, however, this is no longer a barrier. Clinicians may choose to include this condition or any of the conditions below that either have treatment or may be difficult to diagnose. The genes below can be included at no additional charge.

SLC6A8 is associated with creatine transporter deficiency.

SLC6A8

Add-on glucose transporter type 1 deficiency gene (1 gene)

SLC2A1 is the gene associated with GLUT1 deficiency.

SLC2A1

Add-on glycine encephalopathy genes (3 genes)

AMT, GCSH, and GLDC are associated with glycine encephalopathy.

AMT GCSH GLDC

Add-on mucopolysaccharidosis type II gene (1 gene)

IDS is the gene associated with MPS-II.

IDS

Add-on Niemann-Pick type C genes (2 genes)

NPC1 and NPC2 are the genes associated with Niemann-Pick type C.

NPC1 NPC2

Add-on pyridoxal 5'-phosphate-dependent epilepsy gene (1 gene)

PNPO is the gene associated with pyridoxal 5’-phosphate-dependent epilepsy.

PNPO

Add-on pyridoxine-responsive epilepsy gene (1 gene)

ALDH7A1 is associated with pyridoxine-responsive epilepsy.

ALDH7A1

Add-on Smith-Lemli-Opitz syndrome gene (1 gene)

DHCR7 is the gene associated with Smith-Lemli-Opitz syndrome.

DHCR7

  • aminoacidopathies
    • classic homocystinuria due to cystathionine beta-synthase deficiency (CBS)
    • hypermethioninemia
    • hyperprolinemia
    • maple syrup urine disease
    • phenylketonuria (PKU)
    • tetrahydrobiopterin (BH4) cofactor deficiencies
    • tyrosinemia type I
  • cystic fibrosis
  • fatty-acid oxidation disorders
    • carnitine-acylcarnitine translocase (CACT) deficiency
    • carnitine palmitoyl transferase type I (CPT I) deficiency
    • carnitine palmitoyltransferase type II (CPT II) deficiency
    • long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
    • medium chain acyl-CoA dehydrogenase (MCAD) deficiency
    • medium/short chain acyl-CoA dehydrogenase (M/SCHAD) deficiency
    • multiple acyl-CoA dehydrogenase deficiency (MADD aka glutaric acidemia type II)
    • short chain acyl-CoA (SCAD) dehydrogenase deficiency
    • short-branched chain acyl-CoA dehydrogenase (SBCAD) deficiency
    • systemic primary carnitine deficiency
    • trifunctional protein (TFP) deficiency
    • very long chain acyl-CoA dehydrogenase (VLCAD) deficiency
  • galactosemia
    • galactosemia caused by GALT deficiency
    • galactosemia caused by epimerase deficiency
    • galactosemia caused by kinase deficiency
  • glucose-6-phosphate dehydrogenase deficiency (G6PD)
  • glutathione synthetase deficiency
  • lysosomal storage disorders
    • Fabry disease
    • Pompe disease
  • organic acidemias
    • 2-methyl-3-hydroxybutyric aciduria (2M3HBA)
    • 3-hydroxy-3-methylglutaryl-CoA (3HMG) lyase deficiency
    • 3-methylcrotonyl CoA carboxylase (3MCC) deficiency
    • 3-methylglutaconic acidemia type I
    • 3-methylglutaconyl-CoA hydratase deficiency
    • 3-hydroxy-3-methylglutaryl-CoA lyase (3HMG) deficiency
    • Barth syndrome
    • beta-ketothiolase deficiency
    • biotinidase deficiency
    • Canavan disease
    • cobalamin A deficiency
    • cobalamin C deficiency
    • cobalamin D deficiency
    • cobalamin E deficiency
    • ethylmalonic encephalopathy
    • glutamate formiminotransferase deficiency (FIGLU)
    • glutaric acidemia type I
    • glutaric aciduria type II – also known as multiple acyl-CoA dehydrogenase deficiency
    • glutathione synthetase deficiency
    • holocarboxylase synthetase deficiency
    • isobutyryl-CoA dehydrogenase (IBD) deficiency
    • isovaleric acidemia (IVD)
    • malonyl-CoA decarboxylase deficiency
    • maple syrup urine disease (MSUD)
    • methylmalonic acidemia (MUT, MMAA, MMAB)
    • propionic acidemia
    • short-branched chain acyl-CoA dehydrogenase (SBCAD) deficiency
  • urea cycle disorders
    • ALDH18A1-related cutis laxa
    • ALDH18A1-related spastic paraplegia
    • arginase (ARG1) deficiency
    • argininosuccinate lyase (ASL) deficiency
    • carbamoyl phosphate synthetase I (CPSI) deficiency
    • citrin deficiency
    • citrullinemia type I
    • citrullinemia type II
    • gyrate atrophy (OAT)
    • HMG-CoA lyase (HMGCL) deficiency
    • hyperammonemia-hyperornithinemia-homocitrullinuria (HHH) syndrome
    • ornithine aminotransferase (OAT) deficiency
    • ornithine transcarbamylase (OTC) deficiency
  • this panel does not cover tyrosinemia type II, tyrosinemia type III, or rare causes of elevated C5-OH

Inherited metabolic disorders are a group of genetic disorders that result from the deficiency of an enzyme, transporter, or cofactor that is essential to the metabolism of certain substances (protein, carbohydrates, or fats) or that may be essential for the maintenance and health of certain organelles (e.g., lysosomes) in the cell.

Many of these disorders are routinely screened through US NBS programs. Often, early medical intervention—before the onset of symptoms— is crucial to preventing irreversible damage and improving the outcomes of patients who are affected with these disorders.

The majority of metabolic conditions are inherited in an autosomal recessive manner. Ornithine transcarbamylase (OTC) deficiency is inherited in an X-linked manner.

Individually, inherited metabolic disorders are rare disorders, but when they are considered collectively, the incidence of inherited metabolic disorders and cystic fibrosis detected through newborn screening programs may be as common as 1 in 1,600 live births.

This test may be appropriate for:

  • premature infants who may have factors that confound biochemical newborn screening results
  • infants in the neonatal intensive care unit and other symptomatic infants with multiple presumptive positives on newborn screening or traditional biochemical based assays

This test is NOT appropriate for healthy infants.

For considerations for testing please refer to:

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ACAD8 NM_014384.2
ACADM NM_000016.5
ACADS NM_000017.3
ACADSB NM_001609.3
ACADVL NM_000018.3
ACAT1 NM_000019.3
ALDH4A1 NM_003748.3
ALDH7A1 NM_001182.4
ALG1 NM_019109.4
ALG11 NM_001004127.2
ALG12 NM_024105.3
ALG13 NM_001257230.1
ALG2 NM_033087.3
ALG3 NM_005787.5
ALG6 NM_013339.3
ALG8 NM_024079.4
ALG9 NM_024740.2
AMT NM_000481.3
ARG1 NM_000045.3
ARSA NM_000487.5
ASL NM_000048.3
ASPA NM_000049.2
ASS1 NM_000050.4
ATP6V0A2 NM_012463.3
AUH NM_001698.2
B3GLCT NM_194318.3
BCKDHA NM_000709.3
BCKDHB NM_183050.2
BTD NM_000060.3
CBS NM_000071.2
CFTR* NM_000492.3
CHST14 NM_130468.3
COG1 NM_018714.2
COG4 NM_015386.2
COG5 NM_006348.3
COG6 NM_020751.2
COG7 NM_153603.3
COG8 NM_032382.4
CPS1 NM_001875.4
CPT1A NM_001876.3
CPT2 NM_000098.2
DBT NM_001918.3
DECR1 NM_001359.1
DHCR7 NM_001360.2
DOLK NM_014908.3
DPAGT1 NM_001382.3
DPM1 NM_003859.1
DPM2 NM_003863.3
DPM3 NM_153741.1
ETFA NM_000126.3
ETFB NM_001985.2
ETFDH NM_004453.3
ETHE1 NM_014297.3
FAH NM_000137.2
FTCD NM_006657.2
G6PD NM_001042351.2
GAA* NM_000152.3
GALC* NM_000153.3
GALE NM_000403.3
GALK1 NM_000154.1
GALT* NM_000155.3
GCDH NM_000159.3
GCH1 NM_000161.2
GCSH NM_004483.4
GLA* NM_000169.2
GLDC NM_000170.2
HADH NM_005327.4
HADHA NM_000182.4
HADHB NM_000183.2
HEXA NM_000520.4
HEXB NM_000521.3
HLCS NM_000411.6
HMGCL NM_000191.2
HSD17B10 NM_004493.2
IDS NM_000202.6
IVD NM_002225.3
MAT1A NM_000429.2
MCCC1 NM_020166.4
MCCC2 NM_022132.4
MGAT2 NM_002408.3
MLYCD NM_012213.2
MMAA NM_172250.2
MMAB NM_052845.3
MMACHC NM_015506.2
MMADHC NM_015702.2
MOGS NM_006302.2
MPDU1 NM_004870.3
MPI NM_002435.2
MTRR* NM_002454.2
MUT NM_000255.3
NGLY1 NM_018297.3
NPC1 NM_000271.4
NPC2 NM_006432.3
OAT NM_000274.3
OTC NM_000531.5
PAH NM_000277.1
PCBD1 NM_000281.3
PCCA NM_000282.3
PCCB NM_000532.4
PGM1 NM_002633.2
PMM2 NM_000303.2
PNPO NM_018129.3
PRODH NM_016335.4
PTS NM_000317.2
QDPR NM_000320.2
RFT1 NM_052859.3
SLC22A5 NM_003060.3
SLC25A13 NM_014251.2
SLC25A20 NM_000387.5
SLC2A1 NM_006516.2
SLC35A1 NM_006416.4
SLC35A2 NM_001042498.2
SLC35C1 NM_018389.4
SLC6A8 NM_005629.3
SRD5A3 NM_024592.4
TAZ NM_000116.4
TMEM165 NM_018475.4

CFTR: Analysis includes the intronic variants: NM_000492.3:c.3718-2477C>T (also known as 3849+10kbC>T), c.1210-34TG[12]T[5] (also known as T5TG12), c.1210-34TG[11]T[5] (also known as T5TG11), and c.1679+1634A>G.
GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.
GALC: Analysis includes the large (30 kb) deletion for Krabbe Disease.
GALT: Analysis includes the 5 kb deletion NM_000155.3:c.[-1039_753del; 820+50_*789delinsGAATAGACCCCA] as well as the Duarte variant NM_000155.3: c.-119_-116delGTCA.
GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
MTRR: Analysis includes the intronic variant NM_002454.2:c.903+469T>C.