DNA icon

Aromatic L-amino Acid Decarboxylase Deficiency via the DDC Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8233 DDC 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8233DDC81479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn 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

  • Kym Bliven, PhD

Clinical Features and Genetics

Clinical Features

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare disorder of neurotransmitter metabolism that results in a severe deficit of serotonin and catecholamines. The majority of patients with this disorder display initial clinical symptoms during infancy or early childhood, although a few reported cases did not present until adolescence or adulthood (Brun et al. 2010). Affected individuals may exhibit severe developmental delays, oculogyric crises, hypotonia, dystonia, hypokinesia, difficulties with feeding and speech, and autonomic symptoms such as excessive sweating and/or temperature instability (Brun et al. 2010; Wassenberg et al. 2017). Less frequently, ptosis and/or insomnia have been observed. Individuals with a milder disease course have also been described (Leuzzi et al. 2015).

Genetics

Aromatic L-amino acid decarboxylase (AADC) deficiency is inherited in an autosomal recessive manner due to defects in the DDC gene. DDC encodes for a homodimeric, pyridoxal phosphate-dependent enzyme responsible for the second step in the catecholamine biosynthetic pathway that results in synthesis of the neurotransmitter dopamine. In addition, DDC can also decarboxylate 5-hydroxytryptophan into serotonin (Montioli et al. 2014). As dopamine acts as a precursor for the metabolites epinephrine and norepinephrine, patients lacking DDC activity exhibit a combined deficiency of serotonin, dopamine, epinephrine, and norepinephrine (Wassenberg et al. 2017). At least thirty missense variants, several splicing variants, and several small insertions/deletions have been reported as causative for AADC deficiency (Human Gene Mutation Database).

Due to a founder mutation that results in defective splicing (c.714+4A>T), AADC deficiency may be more prevalent in certain Asian populations, such as the Taiwanese (Lee et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test is expected to be high for patients with a biochemical diagnosis of AADC deficiency. In a cohort of 49 patients with biochemically-diagnosed disease, two probable causative variants in the DDC gene were identified in 46/49 patients (93.9%; Brun et al. 2010). In the remaining three patients, one probable causative variant was identified in DDC.

Testing Strategy

This test provides full coverage of all coding exons of the DDC gene 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

DDC sequencing could be considered in patients with symptoms consistent with AADC deficiency, or patients with a biochemical diagnosis of AADC deficiency. We will also sequence the DDC gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
DDC 107930
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deficiency Of Aromatic-L-Amino-Acid Decarboxylase AR 608643

Citations

  • Brun L. et al. 2010. Neurology. 75:64-71. PubMed ID: 20505134
  • Human Gene Mutation Database (Bio-base).
  • Lee H.F. et al. 2009. European Journal of Paediatric Neurology. 13:135-40. PubMed ID: 18567514
  • Leuzzi V. et al. 2015. JIMD Reports. 15:39-45. PubMed ID: 24788355
  • Montioli R. et al. 2014. Human Molecular Genetics. 23:5429-40. PubMed ID: 24865461
  • Wassenberg T. et al. 2017. Orphanet Journal of Rare Diseases. 12:12. PubMed ID: 28100251

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
×
Copy Text to Clipboard
×