Second-tier newborn screen for tyrosinemia type 1 (HT-1) when primary screen showed nonspecific elevations of tyrosine
Diagnosis of HT-1 when used in conjunction with testing for urine organic acids ,liver function, alpha-fetoprotein, and molecular genetic analysis of FAH
This test is a second-tier newborn screen for tyrosinemia type.
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Blood Spots
Newborn Screen
Newborn Screening
Succinylacetone
TYR
Tyrosinemia I
Tyrosinemia Type I
Tyr-1
HT-1
Hepatorenal tyrosinemia
Whole blood
The preferred test for diagnosis and monitoring of patients with tyrosinemia type 1 is TYRBS / Tyrosinemia Follow Up Panel, Blood Spot.
Submit only 1 of the following specimen types:
Preferred:
Specimen Type: Blood Spot
Supplies: Card - Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Blood Spot Collection Card
Acceptable: Whatman Protein Saver 903 Paper, PerkinElmer 226 (formerly Ahlstrom 226) filter paper, Munktell filter paper, or blood collected in tube containing heparin, ACD or EDTA and dried on filter paper.
Specimen Volume: 2 blood spots
Collection Instructions:
1. At least 1 spot should be complete (ie, unpunched).
2. Do not expose specimen to heat or direct sunlight.
3. Do not stack wet specimens.
4. Keep specimen dry.
5. If collection of a new specimen is necessary, let blood dry on the Blood Spot Collection Card (T493) at ambient temperature in a horizontal position for a minimum of 3 hours.
Specimen Stability Information: Ambient (preferred) 90 days/Refrigerated 90 days/Frozen 90 days
Additional Information:
1. For collection instructions, see Blood Spot Collection Instructions
2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800
Acceptable
Specimen Type: Whole Blood
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Green top (sodium or lithium heparin) and yellow top (ACD)
Specimen Volume: 2 mL
Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Refrigerate (preferred) 4 days/Ambient 4 days
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Blood Spot: 1
Whole Blood: 0.5 mL
Blood spot specimen that shows serum rings or has multiple layers | Reject |
Insufficient specimen | Reject |
Unapproved filter papers | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Whole blood | Varies |
Second-tier newborn screen for tyrosinemia type 1 (HT-1) when primary screen showed nonspecific elevations of tyrosine
Diagnosis of HT-1 when used in conjunction with testing for urine organic acids ,liver function, alpha-fetoprotein, and molecular genetic analysis of FAH
This test is a second-tier newborn screen for tyrosinemia type.
Tyrosinemia type 1 (hepatorenal tyrosinemia, HT-1) is an autosomal recessive condition caused by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). 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. Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3 cyclohexanedione (NTBC) is available and is particularly effective when initiated in newborns. The incidence of HT-1 is approximately 1 in 100,000 live births.
While tyrosine can be determined by routine newborn screening, it is not a specific marker for tyrosinemia type I and often may be associated with common and benign transient tyrosinemia of the newborn. Succinylacetone is a specific marker for HT-1 but not consistently measured by newborn screening programs. This assay determines succinylacetone and tyrosine in newborn blood spots by tandem mass spectrometry. Additional follow-up testing may include confirmatory molecular analysis of the FAH gene.
SUCCINYLACETONE
<1.00 nmol/mL
TYROSINE
<4 weeks: 40.0-280.0 nmol/mL
> or =4 weeks: 25.0-150.0 nmol/mL
Elevations of succinylacetone (SUAC) above the reference range with or without elevations of tyrosine (TYR) are indicative of tyrosinemia type 1.
Elevations of TYR above the reference range without elevations of SUAC may be suggestive of tyrosinemia type II, type III, transient hypertyrosinemia of the neonate, or nonspecific liver disease.
Normal levels may be seen in affected individuals undergoing treatment.
In rare cases of tyrosinemia type I, tyrosine and/or succinylacetone may not be elevated.
1. Larochelle J, Alvarez F, Bussieres JF, et al: Effects of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Quebec. Mol Genet Metab. 2012 Sep;107(1-2):49-54
2. Sniderman King L, Trahms C, Scott CR: Tyrosinemia Type I. In: MP Adam, HH Ardinger, PA Pagon et al, eds: GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated May 25, 2017. Accessed January 6, 2022. Available at: www.ncbi.nlm.nih.gov/books/NBK1515/
3. De Jesus VR, Adam BW, Mandel D, Cuthbert CD, Matern D: Succinylacetone as primary marker to detect tyrosinemia type I in newborns and its measurement by newborn screening programs. Mol Genet Metab. 2014 Sept- Oct;113(1-2)67-75
4. 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
5. Chinsky JM, Singh R, Ficicioglu C et al: Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med. 2017 Aug;19(12) doi: 10.1038/gim.2017.101
A 3-mm disk is punched out of the dried blood spot onto a 96-well plate. Then, tyrosine is extracted by the addition of methanol and a known concentration of isotopically labeled tyrosine 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 tyrosine extract. Analytes are measured by liquid chromatography tandem mass spectrometry .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)
Monday through Friday
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.
84510
82542
82542 (if appropriate for government payers)
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
SUAC | Succinylacetone, BS | 53231-7 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
22714 | Interpretation | 59462-2 |
22716 | Reviewed By | 18771-6 |
607629 | Succinylacetone | 53231-7 |
607630 | Tyrosine | 35571-9 |