Organic Aciduria Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10391 ACADSB 81479,81479 Order Options and Pricing
ACAT1 81479,81479
ACSF3 81479,81479
ALDH6A1 81479,81479
AUH 81479,81479
BCKDHA 81405,81479
BCKDHB 81406,81479
CD320 81479,81479
D2HGDH 81479,81479
DBT 81406,81405
DHTKD1 81479,81479
DLD 81406,81479
ECHS1 81479,81479
ETFA 81479,81479
ETFB 81479,81479
ETFDH 81479,81479
GCDH 81406,81479
GSS 81479,81479
HADHA 81406,81479
HIBCH 81479,81479
HLCS 81406,81479
HMGCL 81479,81479
HSD17B10 81479,81479
IDH2 81403,81479
IVD 81406,81479
L2HGDH 81479,81479
MCCC1 81406,81479
MCCC2 81406,81479
MCEE 81479,81479
MLYCD 81479,81479
MMAA 81405,81479
MMAB 81405,81479
MMACHC 81404,81479
MMADHC 81479,81479
MMUT 81406,81479
OXCT1 81479,81479
PCCA 81406,81405
PCCB 81406,81479
SERAC1 81479,81479
SLC25A1 81479,81479
TMEM70 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10391Genes x (41)81479 81403, 81404, 81405, 81406, 81479 $930 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

The organic acidurias (OAs) are a heterogeneous group of disorders characterized biochemically by the accumulation of non-amino organic acids in the urine and blood (Kölker et al. 2013. PubMed ID: 23512157). OAs arise as a result of a defect in an enzyme or transport protein that typically plays a role in one of the metabolic pathways required for the catabolism of amino acids, carbohydrates, or lipids (Villani et al. 2017. PubMed ID: 27613073). Although newborns appear clinically unaffected, onset of symptoms often occurs within hours to months of birth in many patients (Burton. 1998. PubMed ID: 9832597). Other patients may remain asymptomatic in the early years, instead presenting with a late-onset or intermittent form of disease (Burton. 1998. PubMed ID: 9832597; Villani et al. 2017. PubMed ID: 27613073). 

The clinical presentations of OAs can vary, but include lethargy that may progress to coma without quick treatment, feeding difficulties, failure to thrive, developmental delays, seizures, abnormalities in muscle tone, movement disorders, cardiomyopathy, optic nerve atrophy, abnormalities of the basal ganglia and liver, pancreatitis, respiratory distress, and vomiting due to protein intolerance. Biochemically, these patients experience persistent overwhelming or intermittent episodic occurrences of metabolic decompensation, during which metabolic acidosis with an increased anion gap is observed. This may be accompanied by ketoacidosis, lactic acidosis, and hyperammonemia (Burton. 1998. PubMed ID: 9832597; Kölker et al. 2013. PubMed ID: 23512157; Villani et al. 2017. PubMed ID: 27613073; Dimitrov et al. 2021. 32412122). During episodes of decompensation, affected individuals are at risk of developing irreversible, life-threatening organ damage unless treated quickly (Kölker et al. 2013. PubMed ID: 23512157). 

Only one of the genes in this panel (HSD17B10, associated with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency) is inherited in an X-linked manner. Both males and females with pathogenic HSD17B10 variants may be affected, although females tend to be more mildly affected and may also be asymptomatic (Zschocke. 2012. PubMed ID: 22127393). 

Although the individual OAs are rare disorders, collectively the incidence of OAs is estimated at between ~1/3,000-12,500 (Villani et al. 2017. PubMed ID: 27613073; Waters et al. 2018. PubMed ID: 30479748). 

Molecular testing is useful to confirm the genetic cause of a clinical diagnosis, which may then be used for determining appropriate treatment measures, assessment of recurrence risks, and appropriate screening for potential future symptoms.

Genetics

This sequencing panel includes genes that have been associated with organic acidurias or disorders with overlapping clinical symptoms. The majority of the disorders due to defects in these genes are inherited in an autosomal recessive manner. The only exception is HSD17B10, which exhibits X-linked inheritance, and DHTKD1, which can exhibit both autosomal dominant and recessive inheritance. Pathogenic defects in the genes in this panel include missense, nonsense, splice site variants, small deletions, small insertions/duplications, small indels, and exon-level large deletions (Human Gene Mutation Database).

The genes included in this test are associated with disorders that can be broadly classified into several categories based on the pathways within the cell that are disrupted:

Disorders of Biotin Metabolism: HLCS

Disorders of Amino Acid Metabolism: ACADSB, ACSF3, ALDH6A1, AUH, BCKDHA, BCKDHB, DBT, DHTKD1, DLD, ECHS1, GCDH, GSS, HIBCH, HMGCL, HSD17B10, IVD, MCCC1, MCCC2, MCEE, MLYCD, MMUT, PCCA, PCCB

Disorders of Cobalamin Metabolism: CD320, MMAA, MMAB, MMACHC, MMADHC

Disorders of Fatty Acid and Ketone Metabolism: ACAT1, HADHA, OXCT1

Disorders of Nuclear Encoded Mitochondrial Genes: SERAC1, SLC25A1, TMEM70

Disorders of Riboflavin Metabolism Regulation: ETFA, ETFB, ETFDH

Disorders Related to the Citric Acid Cycle: D2HGDH, IDH2, L2HGDH

Of the genes included in this test, no large copy number variants (gross deletions or duplications/insertions) have been observed in the ACADSB,   ALDH6A1, CD320, DHTKD1, DLD, ETFB, HIBCH, HSD17B10, MCCC2, MCEE, MMAB, MMADHC, or SLC25A1 genes. Large copy number variants have been reported as a relatively common cause of disease in the BCKDHA, BCKDHB, DBT, HMGCL, L2HGDH, MLYCD, and PCCA genes. Copy number variants have been reported as a more rare cause of disease in the remaining genes on this panel. To our knowledge, de novo variants have not been reported for the genes in this panel.

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this specific grouping of genes is difficult to estimate as we are unaware of any reports in the literature in which these genes have been sequenced together in a patient cohort with suspected organic acidemia as the primary indication for testing. The clinical sensitivity of sequencing the individual genes is high in patient groups with biochemical or enzymatic diagnoses of the relevant disorders. Analytical sensitivity is expected to be high as most variants reported in these genes are detectable via sequencing.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.8% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

For the IDH2 gene, this test only includes sequencing of exon 4 containing the c.418 and c.419 nucleotides, plus 20 bp of flanking DNA on each side. At this time, IDH2 sequence variants not located at nucleotides c.418 or c.419 will not be reported (see the IDH2 gene summary for further details).

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with biochemical or clinical features consistent with an organic aciduria are good candidates for this test.

Diseases

Name Inheritance OMIM ID
2-aminoadipic 2-oxoadipic aciduria AR 204750
2-Methyl-3-Hydroxybutyric Aciduria XL 300438
2-Methylbutyryl-CoA Dehydrogenase Deficiency AR 610006
3 Methylcrotonyl-CoA Carboxylase 1 Deficiency AR 210200
3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency AR 246450
3-Methylcrotonyl CoA Carboxylase 2 Deficiency AR 210210
3-Methylglutaconic Aciduria AR 250950
3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-like Syndrome AR 614739
Alpha-Methylacetoacetic Aciduria AR 203750
Beta-Hydroxyisobutyryl-CoA Deacylase Deficiency AR 250620
Charcot-Marie-Tooth Disease, Type 2Q AD 615025
Combined D-2- and L-2-HydroxyGlutaric Aciduria AR 615182
Combined Malonic And Methylmalonic Aciduria AR 614265
D-2-Alpha Hydroxyglutaric Aciduria AR 600721
D-2-Hydroxyglutaric Aciduria 2 AR 613657
Dihydrolipoamide dehydrogenase deficiency AR 246900
Glutaric Aciduria, Type 1 AR 231670
Glutaric Aciduria, Type 2 AR 231680
Glutathione Synthetase Deficiency Of Erythrocytes, Hemolytic Anemia Due To AR 231900
Gluthathione Synthetase Deficiency AR 266130
Isovaleryl-CoA Dehydrogenase Deficiency AR 243500
L-2-Hydroxyglutaric Aciduria AR 236792
Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency AR 609016
Malonyl-CoA Decarboxylase Deficiency AR 248360
Maple Syrup Urine Disease AR 248600
Methylmalonate Semialdehyde Dehydrogenase Deficiency AR 614105
Methylmalonic Aciduria and Homocystinuria, cblC Type AR 277400
Methylmalonic Aciduria and Homocystinuria, cblD Type AR 277410
Methylmalonic Aciduria Cbla Type AR 251100
Methylmalonic Aciduria Cblb Type AR 251110
Methylmalonic Aciduria Due To Methylmalonyl-CoA Mutase Deficiency AR 251000
Methylmalonic Aciduria Due To Transcobalamin Receptor Defect AR 613646
Methylmalonyl-CoA Epimerase Deficiency AR 251120
Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type 2 AR 614052
Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency AR 616277
Multiple Carboxylase Defiency, Early Onset AR 253270
Propionic Acidemia AR 606054
Succinyl-CoA Acetoacetate Transferase Deficiency AR 245050
Trifunctional Protein Deficiency AR 609015

Related Tests

Name
PGxome®
Disorders of Fatty Acid Oxidation (FAOD) Panel
Disorders Related to Metabolism of Cobalamin, Folate and Homocysteine Panel
Hyperammonemia Panel
Hypoglycemia Panel - Expanded
Metabolic Hypoglycemia Panel

Citations

  • Burton. 1998. PubMed ID: 9832597
  • Dimitrov et al. 2021. PubMed ID: 32412122
  • Human Gene Mutation Database (Bio-base).
  • K├Âlker et al. 2013. PubMed ID: 23512157
  • Villani et al. 2017. PubMed ID: 27613073
  • Waters et al. 2018. PubMed ID: 30479748
  • Zschocke. 2012. PubMed ID: 22127393

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

Disease Resources

The Organic Acidemia Association has useful information for patients and organizes biannual family conferences. More information is available at: https://www.oaanews.org/.

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ORDER OPTIONS

View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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