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 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 (90 genes)

ABCD1 ABCD4 ACAD8 ACADM ACADS ACADSB ACADVL ACAT1 ACSF3 AHCY ALDH4A1 ARG1 ASL ASS1 AUH BCKDHA BCKDHB BTD CBS CD320 CFTR CPS1 CPT1A CPT2 DBT DNAJC19 ETFA ETFB ETFDH ETHE1 FAH FTCD G6PD GAA GALE GALK1 GALT GCDH GCH1 GLA GNMT GSS HADH HADHA HADHB HCFC1 HLCS HMGCL HPD HSD17B10 IDUA IVD LMBRD1 MAT1A MCCC1 MCCC2 MCEE MLYCD MMAA MMAB MMACHC MMADHC MTR MTRR MUT NAGS OAT OPA3 OTC PAH PC PCBD1 PCCA PCCB PPM1K PRODH PTS QDPR SERAC1 SLC22A5 SLC25A13 SLC25A15 SLC25A20 SMPD1 SPR SUCLA2 SUCLG1 TAT TAZ TMEM70

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.
OTC: Analysis includes the intronic variant NM_000531.5:c.540+265G>A.
PC: Analysis includes the intronic variant NM_000920.3:c.1369-29A>G.

Add-on 2,4-dienoyl-CoA Reductase Deficiency Genes (2 genes)

In addition to the primary panel, clinicians can also choose to include DECR1 and NADK2, 2a genes that haves preliminary evidence of association with 2,4-Dienoyl-CoA reductase deficiency. At this time, the association of DECR1 and NADK2 with 2,4-Dienoyl-CoA reductase deficiency remains uncertain, but some clinicians may wish to include genes that may prove to be clinically significant in the future. These genes can be added at no additional charge.

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.

DECR1 NADK2

Add-on Cerebral Creatine Deficiency Genes (3 genes)

GAMT, GATM, and SLC6A8 are the 3 genes associated with cerebral creatine deficiency.

GAMT GATM SLC6A8

Add-on Congenital Disorders of Glycosylation Genes (102 genes)

Many of CDGs can present in the newborn period with findings such as hypotonia, seizures, brain imaging abnormalities, hepatopathy, coagulopathy, microcephaly, as well as others.

ALG1 ALG11 ALG12 ALG13 ALG14 ALG2 ALG3 ALG6 ALG8 ALG9 ATP6V0A2 B3GALNT2 B3GALT6 B3GAT3 B3GLCT B4GALNT1 B4GALT1 B4GALT7 B4GAT1 C1GALT1C1 CHST14 CHST3 CHST6 CHSY1 COG1 COG2 COG4 COG5 COG6 COG7 COG8 DDOST DHDDS DOLK DPAGT1 DPM1 DPM2 DPM3 DSE EOGT EXT1 EXT2 FKRP FKTN G6PC3 GALNT3 GFPT1 GMPPA GMPPB GNE ISPD LARGE1 LFNG MAGT1 MAN1B1 MGAT2 MOGS MPDU1 MPI NGLY1 NUS1 PAPSS2 PGM1 PGM3 PIGA PIGL PIGM PIGN PIGO PIGQ PIGT PIGV PIGW PMM2 POFUT1 POGLUT1 POMGNT1 POMGNT2 POMK POMT1 POMT2 RFT1 RPN2 SEC23A SEC23B SLC26A2 SLC35A1 SLC35A2 SLC35A3 SLC35C1 SLC35D1 SRD5A3 SSR4 ST3GAL3 ST3GAL5 STT3A STT3B TMEM165 TMEM5 TRIP11 TUSC3 XYLT1

FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T as well as the 3 kb retrotransposon insertion in the 3' UTR at c.*4287_*4288ins3062.
SLC26A2: Analysis includes the intronic variant NM_000112.3:c.-26+2T>C.

Add-on Generalized Leukodystrophies (6 genes)

These genes cause 6 disorders, metachromatic leukodystrophy, Canavan disease, GM2-gangliosidosis AB variant, Krabbe disease, Tay Sachs disease, and Sandhoff disease, that can cause early-onset leukodystrophy. 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.

ARSA ASPA GALC GM2A HEXA HEXB

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

Add-on Glucose Transporter Type 1 (GLUT1) Deficiency Gene (1 gene)

SLC2A1 is associated with GLUT1 deficiency.

SLC2A1

Add-on Glycine Encephalopathy Genes (6 genes)

These genes are associated with glycine encephalopathy and/or elevated glycine levels.

AMT GCSH GLDC LIAS NFU1 SLC6A9

Add-on Mucopolysaccharidosis Type II (MPSII) Gene (1 gene)

IDS is associated with MPSII

IDS

Add-on Niemann-Pick Type C Genes (2 genes)

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

NPC1 NPC2

Add-on Pyridoxal 5’-phosphate-dependent Epilepsy Gene (1 gene)

PNPO is 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 associated with Smith-Lemli-Opitz syndrome.

DHCR7

Add-on Cerebrotendinous Xanthomatosis Gene (1 gene)

CYP27A1 is associated with cerebrotendinous xanthomatosis.

CYP27A1

Add-on 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) Synthase Deficiency Gene (1 gene)

HMGCS2 is the gene associated with HMG-CoA synthase deficiency.

HMGCS2

Add-on Neuronal Ceroid Lipofuscinosis Genes (10 genes)

These genes are associated with pediatric forms of neuronal ceroid lipofuscinosis, also known as Batten disease.

ATP13A2 CLN2 (TPP1) CLN3 CLN5 CLN6 CLN8 CTSD KCTD7 MFSD8 PPT1

CLN3: Analysis includes the intronic variant NM_001042432.1; c.461-13G>C.
PPT1: Analysis includes the large, mostly intronic deletion NM_000310.3:c.124+1215_235-102del3627 as well as the intronic variant NM_000310.3:c.125-15T>G.

Add-on Succinyl-CoA:3-ketoacid CoA Transferase (SCOT) Deficiency Gene (1 gene)

OXCT1 is associated with SCOT deficiency.

OXCT1

  • aminoacidopathies
    • classic homocystinuria due to cystathionine beta-synthase deficiency (CBS)
    • hypermethioninemia
    • hyperprolinemia
    • maple syrup urine disease
    • phenylketonuria (PKU)
    • tetrahydrobiopterin (BH4) cofactor deficiencies
    • tyrosinemia types I, II, and III
    • other disorders that can cause elevated amino acids on NBS including pyruvate carboxylase deficiency are also tested
  • 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
    • Mucopolysaccharidosis type I (MPSI)
    • Niemann-Pick disease types A & B
  • 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 C, D, E, F, G, J, X deficiencies
    • 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, MCEE, SUCLA2, SUCLG1)
    • propionic acidemia
    • pyroglutamic aciduria
    • short-branched chain acyl-CoA dehydrogenase (SBCAD) deficiency
    • other disorders that can cause elevations of organic acids including Costeff syndrome, MEGDEL syndrome, TMEM70 defect, and dilated cardiomyopathy with ataxia (DCMA) syndrome are also tested
  • 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
    • N-acetylglutamate synthase (NAGS) deficiency
    • ornithine aminotransferase (OAT) deficiency
    • ornithine transcarbamylase (OTC) deficiency
  • X-linked adrenoleukodystrophy
  • Note: This panel does not include Gaucher disease

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 United States 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. Additionally, identification of disease causing variants can allow for accurate genetic counseling, determination of reproductive risks, recognition of at-risk relatives and carrier testing for family members.

The majority of metabolic conditions are inherited in an autosomal recessive manner. Ornithine transcarbamylase (OTC) deficiency and X-linked adrenoleukodystrophy are 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 (PMID: 22766612).

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.

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
ABCD1 NM_000033.3
ABCD4 NM_005050.3
ACAD8 NM_014384.2
ACADM NM_000016.5
ACADS NM_000017.3
ACADSB NM_001609.3
ACADVL NM_000018.3
ACAT1 NM_000019.3
ACSF3 NM_174917.4
AHCY NM_000687.3
ALDH4A1 NM_003748.3
ALDH7A1 NM_001182.4
ALG1 NM_019109.4
ALG11 NM_001004127.2
ALG12 NM_024105.3
ALG13 NM_001257230.1; NM_001099922.2
ALG14 NM_144988.3
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
ATP13A2 NM_022089.3
ATP6V0A2 NM_012463.3
AUH NM_001698.2
B3GALNT2 NM_152490.4
B3GALT6 NM_080605.3
B3GAT3 NM_012200.3
B3GLCT NM_194318.3
B4GALNT1 NM_001478.4
B4GALT1 NM_001497.3
B4GALT7 NM_007255.2
B4GAT1 NM_006876.2
BCKDHA NM_000709.3
BCKDHB NM_183050.2
BTD NM_000060.3
C1GALT1C1 NM_001011551.2
CBS NM_000071.2
CD320 NM_016579.3
CFTR* NM_000492.3
CHST14 NM_130468.3
CHST3 NM_004273.4
CHST6 NM_021615.4
CHSY1 NM_014918.4
CLN2 (TPP1) NM_000391.3
CLN3* NM_001042432.1
CLN5 NM_006493.2
CLN6 NM_017882.2
CLN8 NM_018941.3
COG1 NM_018714.2
COG2 NM_007357.2
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
CTSD NM_001909.4
CYP27A1 NM_000784.3
DBT NM_001918.3
DDOST NM_005216.4
DECR1 NM_001359.1
DHCR7 NM_001360.2
DHDDS NM_024887.3
DNAJC19 NM_145261.3
DOLK NM_014908.3
DPAGT1 NM_001382.3
DPM1 NM_003859.1
DPM2 NM_003863.3
DPM3 NM_153741.1
DSE NM_013352.3
EOGT NM_173654.2
ETFA NM_000126.3
ETFB NM_001985.2; NM_001014763.1
ETFDH NM_004453.3
ETHE1 NM_014297.3
EXT1 NM_000127.2
EXT2 NM_207122.1
FAH NM_000137.2
FKRP NM_024301.4
FKTN* NM_001079802.1
FTCD NM_006657.2
G6PC3 NM_138387.3
G6PD NM_001042351.2
GAA* NM_000152.3
GALC* NM_000153.3
GALE NM_000403.3
GALK1 NM_000154.1
GALNT3 NM_004482.3
GALT* NM_000155.3
GAMT NM_000156.5
GATM NM_001482.2
GCDH NM_000159.3
GCH1 NM_000161.2
GCSH NM_004483.4
GFPT1 NM_002056.3; NM_001244710.1
GLA* NM_000169.2
GLDC NM_000170.2
GM2A NM_000405.4
GMPPA NM_205847.2
GMPPB NM_021971.2; NM_013334.3
GNE NM_001128227.2
GNMT NM_018960.5
GSS NM_000178.2
HADH NM_005327.4
HADHA NM_000182.4
HADHB NM_000183.2
HCFC1 NM_005334.2
HEXA NM_000520.4
HEXB NM_000521.3
HLCS NM_000411.6
HMGCL NM_000191.2
HMGCS2 NM_005518.3
HPD NM_002150.2
HSD17B10 NM_004493.2
IDS NM_000202.6
IDUA NM_000203.4
ISPD NM_001101426.3
IVD NM_002225.3
KCTD7 NM_153033.4
LARGE1 NM_004737.4
LFNG NM_001040167.1
LIAS NM_006859.3
LMBRD1 NM_018368.3
MAGT1 NM_032121.5
MAN1B1 NM_016219.4
MAT1A NM_000429.2
MCCC1 NM_020166.4
MCCC2 NM_022132.4
MCEE NM_032601.3
MFSD8 NM_152778.2
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
MTR NM_000254.2
MTRR* NM_002454.2
MUT NM_000255.3
NADK2 NM_001085411.2
NAGS NM_153006.2
NFU1 NM_001002755.2
NGLY1 NM_018297.3
NPC1 NM_000271.4
NPC2 NM_006432.3
NUS1 NM_138459.3
OAT NM_000274.3
OPA3 NM_025136.3; NM_001017989.2
OTC* NM_000531.5
OXCT1 NM_000436.3
PAH NM_000277.1
PAPSS2 NM_001015880.1
PC* NM_000920.3
PCBD1 NM_000281.3
PCCA NM_000282.3
PCCB NM_000532.4
PGM1 NM_002633.2
PGM3 NM_001199917.1
PIGA NM_002641.3
PIGL NM_004278.3
PIGM NM_145167.2
PIGN NM_176787.4
PIGO NM_032634.3
PIGQ NM_004204.3
PIGT NM_015937.5
PIGV NM_017837.3
PIGW NM_178517.3
PMM2 NM_000303.2
PNPO NM_018129.3
POFUT1 NM_015352.1
POGLUT1 NM_152305.2
POMGNT1 NM_017739.3
POMGNT2 NM_032806.5
POMK NM_032237.4
POMT1 NM_007171.3
POMT2 NM_013382.5
PPM1K NM_152542.4
PPT1* NM_000310.3
PRODH NM_016335.4
PTS NM_000317.2
QDPR NM_000320.2
RFT1 NM_052859.3
RPN2 NM_002951.4
SEC23A NM_006364.3
SEC23B NM_006363.4
SERAC1 NM_032861.3
SLC22A5 NM_003060.3
SLC25A13 NM_014251.2
SLC25A15 NM_014252.3
SLC25A20 NM_000387.5
SLC26A2* NM_000112.3
SLC2A1 NM_006516.2
SLC35A1 NM_006416.4
SLC35A2 NM_001042498.2
SLC35A3 NM_012243.2
SLC35C1 NM_018389.4
SLC35D1 NM_015139.2
SLC6A8 NM_005629.3
SLC6A9 NM_201649.3
SMPD1 NM_000543.4
SPR NM_003124.4
SRD5A3 NM_024592.4
SSR4 NM_001204526.1
ST3GAL3 NM_006279.3
ST3GAL5 NM_003896.3
STT3A NM_001278503.1
STT3B NM_178862.2
SUCLA2 NM_003850.2
SUCLG1 NM_003849.3
TAT NM_000353.2
TAZ NM_000116.4
TMEM165 NM_018475.4
TMEM5 NM_014254.2
TMEM70 NM_017866.5
TRIP11 NM_004239.4
TUSC3 NM_006765.3
XYLT1 NM_022166.3

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.
CLN3: Analysis includes the intronic variant NM_001042432.1; c.461-13G>C.
FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T as well as the 3 kb retrotransposon insertion in the 3' UTR at c.*4287_*4288ins3062.
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.
OTC: Analysis includes the intronic variant NM_000531.5:c.540+265G>A.
PC: Analysis includes the intronic variant NM_000920.3:c.1369-29A>G.
PPT1: Analysis includes the large, mostly intronic deletion NM_000310.3:c.124+1215_235-102del3627 as well as the intronic variant NM_000310.3:c.125-15T>G.
SLC26A2: Analysis includes the intronic variant NM_000112.3:c.-26+2T>C.