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Pterin-4 alpha-Carbinolamine Dehydratase (PCD) Deficiency via the PCBD1 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
PCBD1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11887PCBD181479 81479,81479 $990 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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 platform).

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

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

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Hyperphenylalaninemias due to tetrahydrobiopterin (BH4) deficiency are a result of a disruption in phenylalanine homeostasis and dopamine and serotonin biosynthesis. These disorders are caused by pathogenic variants in the genes encoding enzymes involved in the biosynthesis or regeneration of BH4. The phenylalanine, tyrosine, and tryptophan hydroxylases all require BH4 as a cofactor, and lack of this cofactor results in secondary hyperphenylalaninemia and, in some disorders, depletion of the neurotransmitters dopamine and serotonin (Blau et al. 2014).

Patients with pterin-4 α-carbinolamine dehydratase (PCD) deficiency, also known as primapterinuria, may be detected via newborn screening due to hyperphenylalaninemia (HPA). In addition to HPA, these patients are also found to have markedly high levels of neopterin in urine, low levels of biopterin, and significant levels of 7-substituted biopterin compounds, mainly primapterin, while CSF pterin and neurotransmitter levels are normal. The increased levels of neopterin and decreased biopterin have resulted in patients being initially misdiagnosed with 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency. Clinically, some patients have presented with neurologic symptoms, such as progressive hypotonia, EEG abnormalities, and delays in motor development (Blau et al. 2014). For reasons that are not understood, hyperphenylalaninemia is transient in PCD deficient patients. Phenylanine levels may rise as high as those observed in classic phenylketonuria patients, but such spikes seem to be temporary and are only observed during infancy. To date, all reported patients have shown normal levels of phenylanine and normal development by early childhood (Citron et al. 1993; Thöny et al. 1998a; Thöny et al. 1998b; Blau et al. 2014).

While PCD deficiency appears to be a primarily transient disorder that can be treated with a low phenylalanine diet in infancy, a few recent reports have suggested that PCD deficiency may lead to development of disease similar to maturity onset diabetes of the young (MODY). This is thought to be due to the fact that PCD has been proposed to be a bifunctional enzyme which also interacts with the HNF1B transcription factor (Blau et al. 2014; Ferrè et al. 2014; Simaite et al. 2014). Defects in the HNF1B gene have been shown to lead to renal cysts and diabetes syndrome (RCAD, also referred to as MODY5). Recommendations in current literature suggest that PCD deficient patients should therefore be monitored for previously unrecognized later onset complications (Ferrè et al. 2014; Simaite et al. 2014).


Pterin-4 α-Carbinolamine Dehydratase deficiency is thought to be inherited in an autosomal recessive manner. The PCBD1 gene (chromosome 10q22, 4 exons) encodes the PCD enzyme. To date, roughly half of the reported pathogenic variants in the PCBD1 are missense, while the remainder are nonsense and small deletions (Human Gene Mutation Database). Pathogenic variants have been reported in exons 2 through 4, although the majority reside in exon 4. While only a small number of patients have been reported in the literature, over 30% of have been homozygous or compound heterozygous for the variant Gln97*, making this the most commonly reported causative variant in the PCBD1 gene to date.

Other inborn errors of BH4 metabolism can present with similar biochemical features and involve 6-pyruvoyl tetrahydropterin synthase (PTS gene), GTP cyclohydrolase I (GCH1 gene), and Dihydropteridine Reductase (QDPR gene) (Blau et al. 2014, Trujillano et al. 2014).

The PCD enzyme is involved in the regeneration of tetrahydrobiopterin (Blau et al. 2014). During the hydroxylation of phenylalanine by the phenylalanine hydroxylase enzyme, the tetrahydrobiopterin (BH4) cofactor is converted to 4α-carbinolaminetetryhydrobiopterin. This compound is subsequently converted to quinoid dihydrobiopterin via the activity of the PCD enzyme. Finally, the Dihydropteridine Reductase (DHPR) enzyme converts the q-dihydrobiopterin back to tetrahydrobiopterin (Citron et al. 1993; Blau et al. 2014). In addition, the PCD enzyme is also thought to act as a dimerization cofactor (and is thus sometimes called DCoH) for the transcription factor HNF-1α, and is thought to stimulate activity of this transcription factor (Blau et al. 2014; Ferrè et al. 2014; Simaite et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity is difficult to estimate because only a small number of patients have been reported. Analytical sensitivity should be high because all of the variants reported to date are detectable by direct sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the PCBD1 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

Patients with newborn screening results indicative of hyperpheylalaninemia, high urinary neopterin, low urinary biopterin and high levels of primapterin are good candidates for this test, as are patients with decreased/absent pterin-4 α-carbinolamine dehydratase activity. Family members of patients who have known PCBD1 variants are candidates. We will also sequence the PCBD1 gene to determine carrier status.


Official Gene Symbol OMIM ID
PCBD1 126090
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
BH4-Deficient Hyperphenylalaninemia D AR 264070

Related Tests

Hyperphenylalaninemia Panel
Hypomagnesemia Panel


  • Blau N.et al. 2014. Disorders of Tetrahydrobiopterin and Related Biogenic Amines. Online Metabolic & Molecular Bases of Inherited Disease, New York, NY: McGraw-Hill.
  • Citron BA. et al. 1993. American Journal of Human Genetics. 53: 768-74. PubMed ID: 8352282
  • Ferrè S. et al. 2014. Journal of the American Society of Nephrology : Jasn. 25: 574-86. PubMed ID: 24204001
  • Simaite D. et al. 2014. Diabetes. 63: 3557-64. PubMed ID: 24848070
  • Thöny B. et al. 1998. American Journal of Human Genetics. 62: 1302-11. PubMed ID: 9585615
  • Thöny B. et al. 1998. Human Genetics. 103: 162-7. PubMed ID: 9760199
  • Trujillano D. et al. 2014. European Journal of Human Genetics : Ejhg. 22: 528-34. PubMed ID: 23942198


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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