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).

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.


<4 weeks: 40.0-280.0 nmol/mL

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



27.0-107.0 nmol/mL



11.0-45.0 nmol/mL



<1.00 nmol/mL



<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