Invitae Organic Acidemias Panel


Test description

The Invitae Organic Acidemias Panel analyzes 31 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 (31 genes)


2-methyl-3-hydroxybutyric aciduria (2M3HBA), 3-methylcrotonyl-CoA carboxylase (3MCC) deficiency, 3-methylglutaconic acidemia type I, 3-hydroxy-3-methylglutaryl-CoA lyase (3HMG) deficiency, Barth syndrome, beta-ketothiolase deficiency, biotinidase deficiency, Canavan disease, cobalamin A deficiency, cobalamin B deficiency, cobalamin C deficiency, cobalamin D deficiency, ethylmalonic encephalopathy, glutamate formiminotransferase deficiency (FIGLU), glutathione synthetase deficiency, glutaric acidemia type I, holocarboxylase synthetase deficiency, isobutyryl-CoA dehydrogenase (IBD) deficiency, isovaleric acidemia (IVD), malonic acidemia, maple syrup urine disease (MSUD), methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency, multiple acyl-CoA dehydrogenase deficiency (a.k.a. glutaric aciduria type II), propionic acidemia, short-branched chain acyl-CoA dehydrogenase (SBCAD) deficiency

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
ASPA NM_000049.2
AUH NM_001698.2
BCKDHA NM_000709.3
BCKDHB NM_183050.2
BTD NM_000060.3
DBT NM_001918.3
ETFA NM_000126.3
ETFB NM_001985.2
ETFDH NM_004453.3
ETHE1 NM_014297.3
FTCD NM_006657.2
GCDH NM_000159.3
GSS NM_000178.2
HLCS NM_000411.6
HMGCL NM_000191.2
HSD17B10 NM_004493.2
IVD NM_002225.3
MCCC1 NM_020166.4
MCCC2 NM_022132.4
MLYCD NM_012213.2
MMAA NM_172250.2
MMAB NM_052845.3
MMACHC NM_015506.2
MMADHC NM_015702.2
MUT NM_000255.3
PCCA NM_000282.3
PCCB NM_000532.4
TAZ NM_000116.4