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  • Test code: 06191
  • 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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Invitae Organic Acidemias Panel

Test description

The Invitae Organic Acidemias Panel analyzes up to 56 genes that are associated with organic acidemia. This panel may be appropriate for patients who have the signs and symptoms of an organic acidemia, including increased levels of urine organic acids, metabolic acidosis with increased anion gap, and metabolic decompensation during periods of illness, fasting, trauma, or surgery. Sick infants may present as if they have sepsis. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions.

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Primary panel (49 genes)

ACAD8 ACADSB ACAT1 ACSF3 ASPA AUH BCKDHA BCKDHB BTD D2HGDH DBT DNAJC19 ETFA ETFB ETFDH ETHE1 FBP1 FTCD GCDH GSS HIBCH HLCS HMGCL HSD17B10 IDH2 IVD L2HGDH MCCC1 MCCC2 MCEE MLYCD MMAA MMAB MMACHC MMADHC MUT OPA3 OPLAH OXCT1 PCCA PCCB POLG PPM1K SERAC1 SLC25A1 SUCLA2 SUCLG1 TAZ TMEM70

Add-on Kreb Cycle Defect Genes (7 genes)

The inherited disorders of Kreb cycle metabolism will cause elevations of Kreb cycle intermediates on urine organic acid analysis. Young infants and urine samples that are very dilute will also have elevations of Kreb cycle intermediates on urine organic acid analysis. Given the elevations that can arise on urine organic acid analysis, analyzing the genes associated with these disorders may be appropriate. These genes can be included at no additional charge.

DHTKD1 DLD FH NFU1 OGDH SLC13A5 SLC25A19

Gene Disorder
ACAD8 isobutyryl-CoA dehydrogenase (IBD) deficiency
ACADSB short-branched chain acyl-CoA dehydrogenase (SBCAD) deficiency
ACAT1 beta-ketothiolase deficiency
ACSF3 combined malonic and methylmalonic aciduria
ASPA Canavan disease
AUH 3-methylglutaconic acidemia type I
BCKDHA maple syrup urine disease (MSUD)
BCKDHB maple syrup urine disease (MSUD)
BTD biotinidase deficiency
D2HGDH D-2-hydroxyglutaric aciduria type I
DBT maple syrup urine disease (MSUD)
DNAJC19 dilated cardiomyopathy with ataxia syndrome (causes 3-methylglutaconic aciduria)
ETFA multiple acyl-CoA dehydrogenase deficiency (a.k.a. glutaric aciduria type II)
ETFB multiple acyl-CoA dehydrogenase deficiency (a.k.a. glutaric aciduria type II)
ETFDH multiple acyl-CoA dehydrogenase deficiency (a.k.a. glutaric aciduria type II)
ETHE1 ethylmalonic encephalopathy
FBP1 fructose 1,6-Bisphosphatase deficiency
FTCD glutamate formiminotransferase deficiency (FIGLU
GCDH glutaric acidemia type I
GSS glutathione synthetase deficiency
HIBCH 3-hyroxyisobutyryl-CoA hydrolase deficiency
HLCS holocarboxylase synthetase deficiency
HMGCL 3-hydroxy-3-methylglutaryl-CoA lyase (3HMG) deficiency
HSD17B10 2-methyl-3-hydroxybutyric aciduria (2M3HBA)
IDH2 D-2-hydroxyglutaric aciduria type II
IVD isovaleric acidemia (IVD)
L2HGDH L-2-hydroxyglutaric aciduria
MCCC1 3-methylcrotonyl-CoA carboxylase (3MCC) deficiency
MCCC2 3-methylcrotonyl-CoA carboxylase (3MCC) deficiency
MCEE methylmalonic acidemia
MLYCD malonic acidemia
MMAA cobalamin A deficiency
MMAB cobalamin B deficiency
MMACHC cobalamin C deficiency
MMADHC cobalamin D deficiency
MUT methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency
OPA3 Costeff syndrome / 3-methylglutaconic aciduria type III
OPLAH 5-oxoprolinase deficiency
OXCT1 SCOT deficiency
PCCA propionic acidemia
PCCB propionic acidemia
POLG causes 3-methylglutaconic aciduria
PPM1K maple syrup urine disease (MSUD), variant type
SERAC1 Megdel Syndrome
SLC25A1 D,L-2-hydroxyglutaric aciduria
SUCLA2 succinate-CoA ligase deficiency, methylmalonic aciduria
SUCLG1 succinate-CoA ligase deficiency, methylmalonic aciduria
TAZ Barth syndrome
TMEM70 causes 3-methylglutaconic aciduria

Organic acidemias are a group of inherited metabolic disorders that are caused by a disruption of intermediary metabolism. Deficiencies or absence of specific enzymes involved in amino acid metabolism (particularly branched-chain amino acid metabolism) lead to increased accumulation of toxic intermediates called organic acids. The increased amounts of organic acids are detectable in the urine by urine organic acid analysis. The main types of organic acidemia are methylmalonic acidemia, propionic acidemia, isovaleric acidemia, and maple syrup urine disease. Affected infants often present with poor feeding, hypotonia, abnormal liver function tests, neutropenia, unusual odor, vomiting, metabolic acidosis with increased anion gap, ketoacidosis, seizures, and lethargy progressing to coma or death if untreated. Secondary hypoglycemia, carnitine deficiency, and hyperammonemia may also be present. Some patients may also have cardiomyopathy or pancreatitis. Early diagnosis is crucial to avoid neurologic involvement and death. Many organic acidemias have characteristic profiles on urine organic acid analysis. Some patients may only excrete the biochemical abnormalities during metabolic crisis and others may be low excretors; in these cases, molecular testing may be needed to make the diagnosis.

The majority of the organic acidemias are inherited in an autosomal recessive fashion. 2-methyl-3-hydroxybutyric aciduria is inherited in an X-linked manner.

The organic acidemias are individually rare, with incidences ranging between 1 in 50,000 and 1 in 100,000 births. Collectively, the incidence has been reported at 1 in 7,400 newborns. Certain ethnicities may have a higher prevalence for organic acidemias.

This test is appropriate for:

  • patients who present with lethargy, hypotonia, metabolic acidosis with increased anion gap, and ketoacidosis, with or without hyperammonemia
  • patients with nonspecific findings on urine organic acid analysis, in whom an organic acidemia is still suspected

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
ACADSB NM_001609.3
ACAT1 NM_000019.3
ACSF3 NM_174917.4
ASPA NM_000049.2
AUH NM_001698.2
BCKDHA NM_000709.3
BCKDHB NM_183050.2
BTD NM_000060.3
D2HGDH NM_152783.4
DBT NM_001918.3
DHTKD1 NM_018706.6
DLD NM_000108.4
DNAJC19 NM_145261.3
ETFA NM_000126.3
ETFB NM_001985.2; NM_001014763.1
ETFDH NM_004453.3
ETHE1 NM_014297.3
FBP1 NM_000507.3
FH NM_000143.3
FTCD NM_006657.2
GCDH NM_000159.3
GSS NM_000178.2
HIBCH NM_014362.3
HLCS NM_000411.6
HMGCL NM_000191.2
HSD17B10 NM_004493.2
IDH2 NM_002168.3
IVD NM_002225.3
L2HGDH NM_024884.2
MCCC1 NM_020166.4
MCCC2 NM_022132.4
MCEE NM_032601.3
MLYCD NM_012213.2
MMAA NM_172250.2
MMAB NM_052845.3
MMACHC NM_015506.2
MMADHC NM_015702.2
MUT NM_000255.3
NFU1 NM_001002755.2
OGDH NM_002541.3
OPA3 NM_025136.3; NM_001017989.2
OPLAH NM_017570.4
OXCT1 NM_000436.3
PCCA NM_000282.3
PCCB NM_000532.4
POLG NM_002693.2
PPM1K NM_152542.4
SERAC1 NM_032861.3
SLC13A5 NM_177550.4
SLC25A1 NM_005984.4
SLC25A19 NM_021734.4
SUCLA2 NM_003850.2
SUCLG1 NM_003849.3
TAZ NM_000116.4
TMEM70 NM_017866.5