Test ID: PKU
Phenylalanine and Tyrosine, Plasma
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Monitoring effectiveness of dietary therapy in patients with hyperphenylalaninemia*
*This test is useful for monitoring known patients, but is not sufficient to establish a diagnosis
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Phenylketonuria: Evaluation of patients with hyperphenylalaninemia or monitoring effectiveness of dietary therapy. Not sufficient follow-up for abnormal newborn screening results, because other causes of hyperphenylalaninemia (eg, BH4 deficiency) cannot be excluded by this test alone.
Tyrosinemia, type I: For medical management.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
PKU (Phenylketonuria)
Tyrosine
Tyrosinemia
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Collection Container/Tube:
Preferred: Green top (sodium heparin)
Acceptable: Lavender top (EDTA)
Submission Container/Tube: Plastic vial
Specimen Volume: 0.5 mL
Collection Instructions: Fasting (4 hours or more in infants)
Additional Information:
1. Patient's age is required.
2. Include family history, clinical condition (asymptomatic or acute episode), diet, and drug therapy information.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross OK |
| Lipemia | Mild OK; Gross OK |
| Icterus | Mild OK; Gross OK |
| Other | Thrombin-activated tube |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Plasma | Frozen (preferred) | 14 days |
| Refrigerated | 14 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Phenylketonuria (PKU) is the most frequent inherited disorder of amino acid metabolism (about 1:10,000-1:15,000) and was the first successfully treated inborn error of metabolism. It is inherited in an autosomal recessive manner and is caused by a defect in the enzyme phenylalanine hydroxylase (PAH), which converts the essential amino acid phenylalanine to tyrosine, a precursor of dopamine, catecholamines, melanin, and thyroxine. Deficiency of PAH results in decreased levels of tyrosine and an accumulation of phenylalanine in blood and tissues. Untreated, PKU leads to severe brain damage with intellectual impairment, behavior abnormalities, seizures, and spasticity. The level of enzyme activity differentiates classic PKU (PAH activity <1%) from other milder forms; however, all are characterized by increased levels of phenylalanine (hyperphenylalanemia). Treatment includes the early introduction of a diet low in phenylalanine.
Tetrahydrobiopterin (BH4) is a cofactor of not only PAH, but also of the tyrosine and tryptophan hydroxylases. Approximately 2% of patients with hyperphenylalanemia have a deficiency of BH4, which causes a secondary deficit of the neurotransmitters dopamine and serotonin. There are 4 autosomal-recessive disorders associated with BH4 deficiency plus hyperphenylalanemia, guanosine triphosphate cyclohydrolase deficiency, 6-pyruvoyl tetrahydropterine synthase deficiency, dihydropteridine reductase deficiency, and pterin-4 alpha carbinolamine dehydratase (PCD) deficiency. This group of disorders, with the exception of PCD, is characterized by progressive dystonia, truncal hypotonia, extremity hypertonia, seizures, and mental retardation though milder presentations exist. PCD has no symptoms other than transient alterations in tone. Treatment may include administration of BH4, L-dopa (and carbidopa) 5-hydroxytryptophan supplements, and a low phenylalanine diet.
Tyrosine is a nonessential amino acid that derives from dietary sources, the hydroxylation of phenylalanine, or protein breakdown. Primary (PKU) and secondary (defects of BH4 metabolism) hyperphenylalaninemia can cause abnormally low levels of tyrosine. Measurement of the phenylalanine:tyrosine ratio is helpful in monitoring appropriate nutritional intake.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
PHENYLALANINE
Premature: 98-213 nmol/mL
0-31 days: 38-137 nmol/mL
1-24 months: 31-75 nmol/mL
2-18 years: 26-91 nmol/mL
> or =19 years: 35-85 nmol/mL
Conversion Formulas:
Result in mg/dL x 60.6=result in nmol/mL
Result in nmol/mL x 0.0165=result in mg/dL
TYROSINE
Premature: 147-420 nmol/mL
0-31 days: 55-147 nmol/mL
1-24 months: 22-108 nmol/mL
2-18 years: 24-115 nmol/mL
> or =19 years: 34-112 nmol/mL
Conversion Formulas:
Result in mg/dL x 55.6=result in nmol/mL
Result in nmol/mL x 0.0181=result in mg/dL
See Inborn Errors of Amino Acid Metabolism in Special Instructions.
Interpretation Provides information to assist in interpretation of the test results
The quantitative results of phenylalanine and tyrosine with age-dependent reference values are reported without added interpretation. When applicable, reports of abnormal results may contain an interpretation based on available clinical interpretation.
A phenylalanine:tyrosine ratio higher than 3 is considered abnormal.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The determination of plasma phenylalanine and tyrosine levels is not sufficient follow-up for abnormal newborn screening results, because other causes of hyperphenylalaninemia (eg, tetrahydrobiopterin deficiency) cannot be excluded by this test alone.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Mitchell GA, Grompe M, Tanguay RM: Hypertyrosinemia. In The Metabolic and Molecular Bases of Inherited Disease. 8th edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp 1777-1806
2. Scriver CR, Kaufman S: Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. In The Metabolic and Molecular Bases of Inherited Disease. 8th edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp 1667-1724
3. Burgard P, Luo X, Hoffmann GF: Phenylketonuria. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York, NY,McGraw-Hill Medical Division, 2009, pp 163-168
4. Blau N, Thony B: Hyperphenylalanemias: Disorders of Tetrahydrobiopterin Metabolism. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York, NY, McGraw-Hill Medical Division, 2009, pp 169-175
Method Description Describes how the test is performed and provides a method-specific reference
Five mcL of plasma is combined with 195 mcL of water:methanol (50:50; v:v) containing deuterium (2H, denoted herein as 'd') labeled d5-Phe and d4-Tyr internal standards (IS). The mixture is vortexed and spun at 13,000 RPM for 2 minutes to precipitate protein. The supernatant is transferred to a glass vial and introduced into the API 3200 tandem mass spectrometer (MS/MS). The MS/MS is operated in the selected reaction monitoring (SRM) mode to follow the precursor to product ion transitions m/z 166.2 to 120.1 for Phe, m/z 171.2 to 125.1 for d5-Phe, m/z 182.2 to 136.2 for Tyr, and m/z 186.2 to 140.2 for d4-Tyr. Chromatography is performed using a C18 (150x4.6mm) column and total analysis time is 15 minutes.
The concentration of Phe is established by comparison of its ion intensity to that of the IS, d5-Phe, and Tyr is established by comparison of its ion intensity to that of the IS, d4-Tyr.
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday; 10:00 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
84030-Phenylalanine
84510-Tyrosine
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 8380 | Phenylalanine, P | 14875-9 |
| 8627 | Tyrosine, P | 20660-7 |
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