Test Catalog

Test Id : TYRSC

Tyrosinemia Follow-Up Panel, Self-Collect, Blood Spot

Useful For
Suggests clinical disorders or settings where the test may be helpful

Monitoring of individuals with tyrosinemia type I (hepatorenal tyrosinemia)

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test is intended for therapeutic monitoring of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cycohexanedione (NTBC; nitisinone) and dietin patients with tyrosinemia type 1 (HT-1).

Highlights

Blood spot specimens for this test are self-collected by the patient to send directly to Mayo Clinic Laboratories via supplied collection kit. For more information, see Specimen Required.

Method Name
A short description of the method used to perform the test

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Tyrosinemia Follow Up Panel, SC, BS

Aliases
Lists additional common names for a test, as an aid in searching

Hepatorenal tyrosinemia

Hereditary tyrosinemia, type I

HT-1

Nitisinone

NTBC

Tyr type 1

Tyr-1

Specimen Type
Describes the specimen type validated for testing

Whole blood

Necessary Information

1. Patient's age is required.

2. Patient’s street address, city, state, zip code, country and home phone are required.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Supplies: Blood Spot Collection-Self Collect (T858)

Container/Tube: Blood Spot Self Collection Card

Specimen Volume: 2 Blood spots

Additional Information:

1. Order test each time the patient is to collect a dried blood specimen at home and mail the specimen directly to Mayo Clinic Laboratories.

2. Order should be placed a minimum of 3 days prior to desired date of collection.

3. Enter patient’s address information for each order created, including street address, city, state abbreviation, zip code, country, and home phone number.

4. For each order, the Blood Spot Collection-Self Collect kit will be mailed directly to the patient for self-collection.

5. See Dried Blood Spot Collection Tutorial for how to collect blood spots: https://vimeo.com/508490782 

 

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 Blood spot

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Blood spot specimen that shows serum rings or has multiple layers Reject
Insufficient specimen Reject
Unapproved filter papers Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Whole blood Ambient (preferred) 90 days FILTER PAPER
Frozen 90 days FILTER PAPER
Refrigerated 90 days FILTER PAPER

Useful For
Suggests clinical disorders or settings where the test may be helpful

Monitoring of individuals with tyrosinemia type I (hepatorenal tyrosinemia)

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test is intended for therapeutic monitoring of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cycohexanedione (NTBC; nitisinone) and dietin patients with tyrosinemia type 1 (HT-1).

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Tyrosinemia type 1 (hepatorenal tyrosinemia: HT-1) is an autosomal recessive condition caused by a deficiency of the enzyme fumarylacetoacetate hydrolase. HT-1 primarily affects the liver, kidneys, and peripheral nerves causing severe liver disease, renal tubular dysfunction, and neurologic crises. If left untreated, most patients die of liver failure in the first years of life, and all are at risk of developing hepatocellular carcinoma (HCC). The incidence of HT-1 is approximately 1 in 100,000 live births.

 

Affected individuals can show a partial response to dietary restriction of phenylalanine and tyrosine, but dietary treatment in conjunction with the administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3 cyclohexanedione (NTBC; nitisinone), an inhibitor of the proximal tyrosinemia pathway, is very effective when initiated in newborns. Outcome data are promising and to date, newborn patients treated with NTBC have not developed acute liver disease, neurologic crises, or HCC.

 

According to treatment guidelines established in 2017, monitoring of blood NTBC concentration and succinylacetone (SUAC) levels along with measuring the dietary intake of amino acids, including tyrosine and phenylalanine are part of an individualized surveillance plan for patients with HT-1.(1) Monthly analysis of SUAC, NTBC concentration, and amino acids is suggested for the first year of life with the same compounds being monitored every 3 months to age 5 years and every 6 months thereafter.

 

The analytes encompassed in this assay satisfy the recommendations for diagnosis and monitoring of HT-1. In particular, for NTBC, the current guidelines recommend 40 nmol/mL to 60 nmol/mL plasma concentration, which corresponds to a target range for NTBC in dried blood spots of 17 nmol/mL to 26 nmol/mL based on a blood to plasma conversion factor of 2.34.(2)

Data from the validation of this assay suggests that NTBC dosing could be individualized while not to exceed DBS levels of 26 nmol/mL.(3)

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.

TYROSINE

<4 weeks: 40.0-280.0 nmol/mL

> or =4 weeks: 25.0-150.0 nmol/mL

 

PHENYLALANINE:

27.0-107.0 nmol/mL

 

METHIONINE:

11.0-45.0 nmol/mL

 

SUCCINYLACETONE:

<1.00 nmol/mL

 

NITISINONE:

<0.7 nmol/mL

Interpretation
Provides information to assist in interpretation of the test results

Quantitative results with reference values are reported without added interpretation. When applicable, reports of abnormal results may contain an interpretation based on available clinical information.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Bornaprine (Sormodrem) may, at least in theory, interfere with accurate measurement of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3 cyclohexanedione (NTBC).

 

In rare cases of tyrosinemia type I, tyrosine or succinylacetone may not be elevated.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Chinsky JM, Singh R, Ficiciolglu C, et. al: Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med. 2017 Dec;19(12). doi: 10.1038/gim.2017.101

2. Laeremans H, Turner C, Andersson T, et al: Inter-laboratory analytical improvement of succinylacetone and nitisinone quantification from dried blood spot samples. JIMD Rep. 2020 May;53(1):90-102

3. Schultz MJ, Netzel BC, Singh RH, et al: Laboratory monitoring of patients with hereditary tyrosinemia type I. Mol Genet Metab. 2020 Aug;130(4):247-254

4. Mitchell GA, Grompe M, Lambert M, Tanguay RM: Hypertyrosinemia. In: Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed January 22, 2021. Available at  https://ommbid.mhmedical.com/content.aspx?sectionid=225082825&bookid=2709

5. Blackburn PR, Hickey RD, Nace RA, et al: Silent tyrosinemia type I without elevated tyrosine or succinylacetone associated with liver cirrhosis and hepatocellular carcinoma. Hum Mutat. 2016 Oct;37(10):1097-1105. doi: 10.1002/humu.23047

Method Description
Describes how the test is performed and provides a method-specific reference

A 3-mm disk is punched out of the blood spot onto a 96-well plate. The amino acids and nitisinone are extracted by the addition of methanol and known concentrations of isotopically labeled amino acids and mesotrione as internal standards. The extract is moved to another 96-well plate and dried under a stream of nitrogen. In a parallel process, succinylacetone is extracted from the residual blood spot by the addition of a methanol solution containing isotopically labeled succinylacetone as internal standard, derivatized with an acidic hydrazine solution, evaporated and combined with the amino acid and nitisinone extract. Analytes are measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of the analytes are established by computerized comparison of ion intensities of these analytes to that of the respective internal standards.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

1 year

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

84510

84030

82131

82542

80299

82542 only (if appropriate for government payers)

 

LOINC® Information

Test Id Test Order Name Order LOINC Value
TYRSC Tyrosinemia Follow Up Panel, SC, BS 94573-3
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip
610503 Tyrosine 35571-9
610504 Phenylalanine 29573-3
610505 Methionine 47700-0
610506 Succinylacetone 53231-7
610507 Nitisinone 85098-2
BG728 Reason for Referral 42349-1
610502 Reviewed By 18771-6
BG729 Patient Street Address 56799-0
BG730 Patient City 68997-6
BG731 Patient State 46499-0
BG732 Patient Zip Code 45401-7
BG741 Patient Country 87721-7
BG733 Patient Home Phone 42077-8

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports