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  • Test code: 06222
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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Invitae Treatable Neurometabolic Disorders Panel

Test description

The Invitae Treatable Neurometabolic Disorders Panel analyzes genes that are associated with inherited neurometabolic disorders that have treatments of varying efficacy. These genes were selected based on the available evidence to date to provide a broad test for treatable inherited neurometabolic disorders. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (195 genes)

ABCD1 ABCD4 ACAT1 AGA ALDH18A1 ALDH3A2 ALDH4A1 ALDH5A1 ALDH7A1 AMN AMT APTX ARG1 ARHGEF9 ARSA ASAH1 ASL ASNS ASPA ASS1 ATAD1 ATP7A ATP7B AUH BCKDHA BCKDHB BSCL2 BSND BTD CA5A CAD CASR CBS CD320 CLCNKB CLDN16 CLDN19 CLN2 (TPP1) CLN3 CLN5 CLN6 CNNM2 COQ2 COQ4 COQ6 COQ7 COQ8A COQ8B COQ9 CP CPOX CPS1 CUBN CYP27A1 DBT DDC DHCR7 DHFR DLAT DLD DNAJC12 EGF ETFA ETFB ETFDH ETHE1 FAM111A FOLR1 FXYD2 GALC GAMT GATM GCDH GCH1 GCLC GIF GLA GLB1 GLDC GLRA1 GLRB GLUD1 GNS GOT2 GPHN GSS GUSB HCFC1 HEXA HEXB HGSNAT HLCS HMBS HMGCL HMGCS2 HNF1B HSD17B10 IDS IDUA IVD KCNA1 KCNJ10 LIPA LMBRD1 MAN2B1 MCCC1 MCCC2 MCEE MFSD8 MLYCD MMAA MMAB MMACHC MMADHC MOCS1 MOCS2 MSMO1 MTHFR MTR MTRR MUT NAGLU NAGS NPC1 NPC2 NT5C3A OAT OTC OXCT1 PAH PANK2 PCBD1 PCCA PCCB PDHA1 PDHB PDHX PDP1 PDSS2 PEX1 PEX10 PEX11B PEX12 PEX13 PEX14 PEX16 PEX19 PEX2 PEX26 PEX3 PEX5 PEX6 PGM3 PHGDH PHYH PNPO PPM1K PRDX1 PROSC PRPS1 PSAT1 PSPH PTS QDPR RAPSN SCN4A SGSH SLC12A1 SLC12A3 SLC13A5 SLC18A2 SLC19A1 SLC19A2 SLC19A3 SLC1A3 SLC25A13 SLC25A15 SLC25A19 SLC2A1 SLC30A10 SLC39A14 SLC39A8 SLC46A1 SLC6A19 SLC6A3 SLC6A5 SLC6A8 SPR TAT TCN1 TCN2 TH TPK1 TRPM6 TTPA

  • X-linked adrenoleukodystrophy (X-ALD)
  • Methylmalonic aciduria and homocystinuria due to cobalamin J (cblJ) deficiency
  • Beta-ketothiolase deficiency
  • Aspartylglucosaminuria
  • ALDH18A1-related conditions:
    • Delta-pyrroline-5-carboxylate synthetase (P5CS) deficiency
    • Cutis laxa (ADCL3 and ARCL3A)
    • Spastic paraplegia (SPG9A and SPG9B)
  • Sjögren-Larsson syndrome
  • Hyperprolinemia Type 2 (HPII)
  • Succinic semialdehyde dehydrogenase deficiency (SSADH)
  • Imerslund-Gräsbeck syndrome
  • Glycine encephalopathy
  • Oculomotor apraxia type I (AOA1)
  • Arginase deficiency
  • Hereditary hyperekplexia, Early infantile epileptic encephalopathy 8 (EIEE8)
  • Metachromatic leukodystrophy
  • ASAH1-related conditions:
    • Farber disease
    • Peripheral osteolysis
    • Polyarticular arthritis and spinal muscular atrophy (SMA)
    • SMA with progressive myoclonic epilepsy (SMAPME)
  • Argininosuccinate lyase deficiency
  • Asparagine synthetase deficiency (ASNS)
  • Canavan disease
  • Citrullinemia type I
  • Hyperekplexia type 4 (HKPX4)
  • Menkes disease (MD), Occipital Horn syndrome (OHS), Charcot-Marie-Tooth distal hereditary motor neuropathy
  • Wilson disease
  • 3-Methylglutaconic aciduria type 1
  • Maple syrup urine disease (MSUD)
  • BSCL2-related conditions:
    • Charcot-Marie-Tooth disease type 2 (CMT2)
    • Distal hereditary motor neuropathy type 5 (HMN5)
    • Spastic paraplegia 17 (SPG17) (Silver syndrome)
    • Congenital generalized lipodystrophy, type 2 (CGL2)
  • BSND-related conditions:
    • Bartter syndrome type 4a (BARTS4A)
    • Non-syndromic deafness
  • Biotinidase deficiency
  • Carbonic anhydrase VA deficiency (CAVA)
  • CAD-related conditions:
    • Early infantile epileptic encephalopathy (EIEE)
    • Autism spectrum disorder with abnormal glycosylation
    • Congenital heart disease with neurodevelopmental disability
  • CASR-related conditions:
    • Familial hypocalciuric hypercalcemia (FHH)
    • Autosomal dominant hypocalcemia (ADH)
    • ADH with Bartter syndrome
    • Neonatal severe hyperparathyroidism (NSHPT)
  • Homocystinuria due to cystathionine beta-synthase (CBS) deficiency
  • CD320-associated transcobalamin receptor deficiency
  • Bartter syndrome type 3 (BSIII)
  • Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC)
  • Neuronal ceroid lipofuscinosis type 3 (CLN3)
  • Neuronal ceroid lipofuscinosis type 5 (CLN5)
  • Neuronal ceroid lipofuscinosis type 6 (CLN6)
  • Hypomagnesemia, seizures and intellectual disability
  • COQ8B-related nephrotic syndrome
  • Aceruloplasminemia
  • Hereditary coproporphyria (HCP), Harderoporphyria
  • Carbamoyl phosphate synthetase 1 (CPS1) deficiency
  • Megaloblastic anemia 1 (MGA1) (Imerslund-Gräsbeck syndrome)
  • Cerebrotendinous xanthomatosis
  • Aromatic L-amino acid decarboxylase deficiency (AADC)
  • Smith-Lemli-Opitz syndrome (SLOS)
  • Megaloblastic anemia due to dihydrofolate reductase deficiency
  • Pyruvate dehydrogenase E2 (PDHE2) deficiency
  • Dihydrolipoamide dehydrogenase deficiency (DLD)
  • Hyperphenylalaninemia (HPA)
  • EGF-related conditions:
    • Renal hypomagnesemia
    • Isolated hypogonadotropic hypogonadism
  • Multiple acyl-CoA dehydrogenase deficiency (MADD) (Glutaric acidemia type II)
  • Ethylmalonic encephalopathy
  • Gracile bone dysplasia; Kenny-Caffey syndrome (KCS)
  • Cerebral folate deficiency
  • FXYD2-related hypomagnesemia
  • Krabbe disease
  • Guanidinoacetate methyltransferase deficiency (GAMT)
  • Cerebral creatine deficiency due to arginine: glycine amidinotransferase deficiency (AGAT)
  • Glutaric acidemia type I
  • Dopa-responsive dystonia (DRD), GTP cyclohydrolase deficiency
  • Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency
  • Intrinsic factor deficiency (IFD)
  • Fabry disease
  • GM1 gangliosidosis, Mucopolysaccharidosis IVb
  • Hyperekplexia type 1 (HKPX1)
  • Hyperekplexia type 2 (HKPX2)
  • Hyperinsulinism-hyperammonemia (HI/HA) syndrome
  • Mucopolysaccharidosis type IIID (MPS IIID) (Sanfilippo syndrome D)
  • Glutathione synthetase deficiency
  • Mucopolysaccharidosis type VII (MPS VII) (Sly syndrome )
  • Cobalamin X (cblX) deficiency
  • Tay-Sachs disease
  • Sandhoff disease
  • HGSNAT-related conditions:
    • Mucopolysaccharidosis IIIC (MPS IIIC) (Sanfilippo syndrome C)
    • Retinitis pigmentosa (RP)
  • Holocarboxylase synthetase deficiency
  • Acute intermittent porphyria (AIP) (Porphobilinogen deaminase deficiency)
  • 3-hydroxy-3-methylglutaryl (HMG)-CoA lyase deficiency
  • 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase deficiency
  • Renal cyst and diabetes syndrome
  • 2-Methyl-3-hydroxybutyric aciduria
  • Mucopolysaccharidosis type II (MPSII) (Hunter syndrome)
  • Mucopolysaccharidosis type I (MPS I) (Hurler-Scheie syndrome)
  • Isovaleric acidemia
  • KCNA1-related conditions:
    • Episodic ataxia type 1 (EA1)
    • Paroxysmal kinesigenic dyskinesia
  • SeSAME syndrome (EAST syndrome)
  • Lysosomal acid lipase (LAL) deficiency, Wolman disease
  • Methylmalonic aciduria with homocystinuria due to cobalamin F deficiency
  • Alpha-mannosidosis
  • 3 Methylcrotonyl-CoA carboxylase deficiency (3MCC)
  • Methylmalonyl-CoA epimerase deficiency
  • Neuronal ceroid lipofuscinosis type 7 (CLN7), Retinal dystrophy
  • Malonyl-CoA decarboxylase deficiency
  • Methylmalonic aciduria cobalamin A type (MMACblA)
  • Methylmalonic aciduria cobalamin B type (MMACblB)
  • Methylmalonic aciduria with homocystinuria due to cobalamin C (cblC) deficiency
  • Methylmalonic aciduria with homocystinuria due to cobalamin D (cblD) deficiency
  • Molybdenum cofactor deficiency
  • Microcephaly, congenital cataract, psoriasiform dermatitis (MCCPD)
  • Severe MTHFR deficiency
  • Cobalamin G (cblG) deficiency
  • Cobalamin E (cblE) deficiency
  • Methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency
  • Mucopolysaccharidosis type IIIB (MPS IIIB) (Sanfilippo syndrome B)
  • N-acetylglutamate synthase deficiency
  • Niemann-Pick disease type C (NPC)
  • Hemolytic anemia due to pyrimidine-5’-nucleosidase type I (P5’N1) deficiency
  • Gyrate atrophy of choroid and retina (GACR)
  • Ornithine transcarbamylase (OTC) deficiency
  • Succinyl CoA:3-oxoacid CoA transferase (SCOT) deficiency
  • Phenylketonuria (PKU)
  • Pantothenate kinase-associated neurodegeneration (PKAN)
  • Tetrahydrobiopterin-deficient hyperphenylalaninemia
  • Propionic acidemia (PA)
  • Pyruvate dehydrogenase E1-alpha (PDHE1α) deficiency
  • Pyruvate dehydrogenase complex (PDHC) deficiency
  • Pyruvate dehydrogenase phosphatase deficiency (PDHPD)
  • Primary coenzyme Q10 deficiency
  • Zellweger spectrum disorder (ZSD)
  • PGM3-congenital disorder of glycosylation (PGM3-CDG)
  • Phosphoglycerate dehydrogenase deficiency
  • Refsum disease
  • Pyridoxal 5’-phosphate-dependent epilepsy
  • PPM1K associated maple urine disease
  • Epi-cobalamin C (epi-cblC) deficiency
  • Pyridoxine-dependent epilepsy
  • PRPS1-related conditions
  • Phosphoserine aminotransferase (PSAT) deficiency, Neu-Laxova syndrome
  • Phosphoserine phosphatase deficiency (PSPHD)
  • Tetrahydrobiopterin-deficient hyperphenylalaninemia due to 6-pyruvate tetrahydropterin synthase deficiency
  • Tetrahydrobiopterin-deficient hyperphenylalaninemia due to dihydropteridine reductase deficiency (DHPR)
  • Congenital myasthenic syndrome 11 (CMS11), Fetal akinesia deformation sequence 2 (FADS2)
  • SCN4A-related conditions:
    • Hypokalemic periodic paralysis type 2 (HOKPP2)
    • Hyperkalemic periodic paralysis (HYPP)
    • Paramyotonia congenita (PMC)
    • Potassium-aggravated myotonia
    • Congenital myopathy
    • Congenital myasthenic syndrome 16 (CMS16)
  • Mucopolysaccharidosis type IIIA (MPS IIIA) (Sanfilippo syndrome A)
  • Bartter syndrome type 1
  • Gitelman syndrome
  • Developmental and epileptic encephalopathy, Early infantile epileptic encephalopathy (EIEE)
  • Brain dopamine-serotonin vesicular transport disease
  • SLC19A1-related myelomeningocele
  • Thiamine-responsive megaloblastic anemia
  • Biotin-responsive basal ganglia disease (BBGD) (Thiamine Metabolism Dysfunction Syndrome 2 (THMD2))
  • Episodic ataxia type 6 (EA6), Developmental delay and/or autism
  • Citrin deficiency
  • Hyperornithinemia-hyperammonemia-homocystinuria (HHH) syndrome
  • Thiamine metabolism dysfunction syndromes
  • Glucose transporter type 1 (GLUT1) deficiency
  • Hypermanganesemia with dystonia
  • Hypomanganesemia with dystonia type 2 (HMNDYT2), Hyperostosis carnialis interna
  • SLC39A8-congenital disorder of glycosylation (SLC39A8-CDG, CDG-IIn)
  • Hereditary folate malabsorption
  • Hartnup disease
  • Infantile parkinsonism-dystonia (PKDYS1) (Dopamine transporter deficiency syndrome)
  • Hyperekplexia 3 (HKPX3)
  • Creatine transporter deficiency (CTD)
  • Sepiapterin reductase deficiency
  • Tyrosinemia type 2
  • Transcobalamin I deficiency
  • Transcobalamin II deficiency
  • Tyrosine hydroxylase deficiency (Segawa syndrome)
  • Thiamine metabolism dysfunction syndrome 5 (THMD5)
  • Neuronal ceroid lipofuscinosis 2 (CLN2)
  • Familial hypomagnesemia with secondary hypocalcemia
  • Ataxia with vitamin E deficiency (AVED)

To view the complete clinical description of this panel, click here.

Neurometabolic disorders follow a variety of inheritance patterns including autosomal recessive, autosomal dominant, and X-linked. Several conditions follow both autosomal recessive and autosomal dominant inheritance. Conditions associated with mitochondrial inheritance and repeat expansions are not evaluated by this panel.

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ABCD1 NM_000033.3
ABCD4 NM_005050.3
ACAT1 NM_000019.3
AGA NM_000027.3
ALDH18A1 NM_002860.3
ALDH3A2 NM_000382.2
ALDH4A1 NM_003748.3
ALDH5A1 NM_001080.3
ALDH7A1 NM_001182.4
AMN* NM_030943.3
AMT NM_000481.3
APTX NM_175073.2
ARG1 NM_000045.3
ARHGEF9 NM_015185.2; NM_001173479.1
ARSA NM_000487.5
ASAH1 NM_177924.3
ASL NM_000048.3
ASNS NM_133436.3
ASPA NM_000049.2
ASS1 NM_000050.4
ATAD1 NM_001321967.1
ATP7A NM_000052.6
ATP7B NM_000053.3
AUH NM_001698.2
BCKDHA NM_000709.3
BCKDHB NM_183050.2
BSCL2 NM_032667.6
BSND NM_057176.2
BTD NM_000060.3
CA5A NM_001739.1
CAD NM_004341.4
CASR NM_000388.3
CBS NM_000071.2
CD320 NM_016579.3
CLCNKB* NM_000085.4
CLDN16 NM_006580.3
CLDN19 NM_148960.2
CLN2 (TPP1) NM_000391.3
CLN3 NM_001042432.1
CLN5 NM_006493.2
CLN6 NM_017882.2
CNNM2 NM_017649.4
COQ2 NM_015697.7
COQ4 NM_016035.4
COQ6 NM_182476.2
COQ7 NM_016138.4
COQ8A NM_020247.4
COQ8B NM_024876.3
COQ9 NM_020312.3
CP NM_000096.3
CPOX NM_000097.5
CPS1 NM_001875.4
CUBN* NM_001081.3
CYP27A1 NM_000784.3
DBT NM_001918.3
DDC* NM_000790.3
DHCR7 NM_001360.2
DHFR NM_000791.3
DLAT NM_001931.4
DLD NM_000108.4
DNAJC12 NM_021800.2
EGF NM_001963.5
ETFA NM_000126.3
ETFB NM_001985.2
ETFDH NM_004453.3
ETHE1 NM_014297.3
FAM111A NM_022074.3
FOLR1 NM_016725.2
FXYD2 NM_001680.4
GALC* NM_000153.3
GAMT NM_000156.5
GATM NM_001482.2
GCDH NM_000159.3
GCH1 NM_000161.2
GCLC NM_001498.3
GIF NM_005142.2
GLA* NM_000169.2
GLB1 NM_000404.2
GLDC NM_000170.2
GLRA1 NM_000171.3
GLRB NM_000824.4
GLUD1 NM_005271.4
GNS NM_002076.3
GOT2 NM_002080.3
GPHN NM_020806.4
GSS NM_000178.2
GUSB NM_000181.3
HCFC1 NM_005334.2
HEXA NM_000520.4
HEXB NM_000521.3
HGSNAT NM_152419.2
HLCS NM_000411.6
HMBS NM_000190.3
HMGCL NM_000191.2
HMGCS2 NM_005518.3
HNF1B NM_000458.3
HSD17B10 NM_004493.2
IDS* NM_000202.6
IDUA NM_000203.4
IVD NM_002225.3
KCNA1 NM_000217.2
KCNJ10 NM_002241.4
LIPA NM_000235.3
LMBRD1 NM_018368.3
MAN2B1 NM_000528.3
MCCC1 NM_020166.4
MCCC2 NM_022132.4
MCEE NM_032601.3
MFSD8 NM_152778.2
MLYCD NM_012213.2
MMAA NM_172250.2
MMAB NM_052845.3
MMACHC NM_015506.2
MMADHC NM_015702.2
MOCS1 NM_001358530.2
MOCS2 NM_176806.3; NM_004531.4
MSMO1 NM_006745.4
MTHFR* NM_005957.4
MTR NM_000254.2
MTRR* NM_002454.2
MUT NM_000255.3
NAGLU NM_000263.3
NAGS NM_153006.2
NPC1 NM_000271.4
NPC2 NM_006432.3
NT5C3A NM_016489.12
OAT* NM_000274.3
OTC* NM_000531.5
OXCT1 NM_000436.3
PAH NM_000277.1
PANK2 NM_153638.2
PCBD1 NM_000281.3
PCCA NM_000282.3
PCCB NM_000532.4
PDHA1 NM_000284.3
PDHB NM_000925.3
PDHX NM_003477.2
PDP1 NM_018444.3
PDSS2 NM_020381.3
PEX1 NM_000466.2
PEX10 NM_153818.1
PEX11B NM_003846.2
PEX12 NM_000286.2
PEX13 NM_002618.3
PEX14 NM_004565.2
PEX16 NM_004813.2
PEX19 NM_002857.3
PEX2 NM_000318.2
PEX26 NM_017929.5
PEX3 NM_003630.2
PEX5 NM_001131025.1
PEX6 NM_000287.3
PGM3 NM_001199917.1
PHGDH NM_006623.3
PHYH NM_006214.3
PNPO NM_018129.3
PPM1K NM_152542.4
PRDX1 NM_002574.3
PROSC NM_007198.3
PRPS1 NM_002764.3
PSAT1 NM_058179.3
PSPH* NM_004577.3
PTS NM_000317.2
QDPR NM_000320.2
RAPSN* NM_005055.4
SCN4A NM_000334.4
SGSH NM_000199.3
SLC12A1 NM_000338.2
SLC12A3 NM_000339.2
SLC13A5 NM_177550.4
SLC18A2 NM_003054.4
SLC19A1 NM_194255.2
SLC19A2 NM_006996.2
SLC19A3 NM_025243.3
SLC1A3 NM_004172.4
SLC25A13 NM_014251.2
SLC25A15 NM_014252.3
SLC25A19 NM_021734.4
SLC2A1 NM_006516.2
SLC30A10 NM_018713.2
SLC39A14 NM_001128431.2; NM_015359.5
SLC39A8 NM_022154.5
SLC46A1 NM_080669.5
SLC6A19 NM_001003841.2
SLC6A3 NM_001044.4
SLC6A5 NM_004211.3
SLC6A8 NM_005629.3
SPR NM_003124.4
TAT NM_000353.2
TCN1 NM_001062.3
TCN2 NM_000355.3
TH NM_199292.2
TPK1 NM_022445.3
TRPM6 NM_017662.4
TTPA NM_000370.3

AMN: Deletion/duplication analysis is not offered for exon 1.
CLCNKB: Deletion/duplication analysis is not offered for this gene.
CUBN: Analysis includes the intronic variant NM_001081.3: c.3330-439C>G.
DDC: Deletion/duplication analysis is not offered for exons 10-11.
GALC: Analysis includes the large (30 kb) deletion for Krabbe Disease. Deletion/duplication analysis is not offered for exon 6.
GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
IDS: Detection of complex rearrangements not offered (PMID: 7633410, 20301451).
MTHFR: The NM_005957.4:c.665C>T (p.Ala222Val) (aka 677C>T) and c.1286A>C (p.Glu429Ala) (aka 1298A>C) variants are not reported in our primary report.
MTRR: Analysis includes the intronic variant NM_002454.2:c.903+469T>C.
OAT: Deletion/duplication analysis is not offered for exon 2.
OTC: Analysis includes the intronic variant NM_000531.5:c.540+265G>A.
PSPH: Deletion/duplication and sequencing analysis is not offered for exons 4-5.
RAPSN: Analysis includes the promoter variants NM_005055.3:c.-210A>G and NM_005055.3:c.-199C>G.