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Laboratory monitoring of patients with hereditary tyrosinemia type I.
Mol Genet Metab. 2020 08; 130(4):247-254.MG

Abstract

BACKGROUND

The prognosis of patients with Hereditary Tyrosinemia Type 1 (HT-1) has greatly improved with early detection through newborn screening and the introduction of nitisinone (NTBC) therapy. A recent guideline calls for periodic monitoring of biochemical markers and NTBC levels to tailor treatment; however, this is currently only achieved through a combination of clinical laboratory tests. We developed a multiplexed assay measuring relevant amino acids, succinylacetone (SUAC), and NTBC in dried blood spots (DBS) to facilitate treatment monitoring.

METHODS

Tyrosine, phenylalanine, methionine, NTBC and SUAC were eluted from DBS with methanol containing internal standards for each analyte and analyzed by liquid chromatography tandem mass spectrometry over 6.5 min in the multiple reaction monitoring positive mode.

RESULTS

Pre-analytical and analytical factors were studied and demonstrated a reliable assay. Chromatography resolved an unknown substance that falsely elevates SUAC concentrations and was present in all samples. To establish control and disease ranges, the method was applied to DBS collected from controls (n = 284) and affected patients before (n = 2) and after initiation of treatment (n = 29). In the treated patients SUAC concentrations were within the normal range over a wide range of NTBC levels.

CONCLUSIONS

This assay enables combined, accurate measurement of revelevant metabolites and NTBC in order to simplify treatment monitoring of patients with HT-1. In addition, the use of DBS allows for specimen collection at home to facilitate more standardization in relation to drug and dietary treatment.

Authors+Show Affiliations

Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA.Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA.Department of Human Genetics and Pediatrics, Emory University, Atlanta, GA, USA.Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA.Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA.Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA.Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA.Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA.Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA.Maine Medical Partners Pediatrics Specialty Care, Portland, ME, USA.Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA. Electronic address: matern@mayo.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32546364

Citation

Schultz, Matthew J., et al. "Laboratory Monitoring of Patients With Hereditary Tyrosinemia Type I." Molecular Genetics and Metabolism, vol. 130, no. 4, 2020, pp. 247-254.
Schultz MJ, Netzel BC, Singh RH, et al. Laboratory monitoring of patients with hereditary tyrosinemia type I. Mol Genet Metab. 2020;130(4):247-254.
Schultz, M. J., Netzel, B. C., Singh, R. H., Pino, G. B., Gavrilov, D. K., Oglesbee, D., Raymond, K. M., Rinaldo, P., Tortorelli, S., Smith, W. E., & Matern, D. (2020). Laboratory monitoring of patients with hereditary tyrosinemia type I. Molecular Genetics and Metabolism, 130(4), 247-254. https://doi.org/10.1016/j.ymgme.2020.06.001
Schultz MJ, et al. Laboratory Monitoring of Patients With Hereditary Tyrosinemia Type I. Mol Genet Metab. 2020;130(4):247-254. PubMed PMID: 32546364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Laboratory monitoring of patients with hereditary tyrosinemia type I. AU - Schultz,Matthew J, AU - Netzel,Brian C, AU - Singh,Rani H, AU - Pino,Gisele B, AU - Gavrilov,Dimitar K, AU - Oglesbee,Devin, AU - Raymond,Kimiyo M, AU - Rinaldo,Piero, AU - Tortorelli,Silvia, AU - Smith,Wendy E, AU - Matern,Dietrich, Y1 - 2020/06/06/ PY - 2020/04/12/received PY - 2020/05/31/revised PY - 2020/06/01/accepted PY - 2020/6/18/pubmed PY - 2020/6/18/medline PY - 2020/6/18/entrez KW - Dried blood spots KW - Hereditary Tyrosinemia type I KW - LC-MS/MS KW - NTBC KW - Nitisinone KW - Succinylacetone SP - 247 EP - 254 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 130 IS - 4 N2 - BACKGROUND: The prognosis of patients with Hereditary Tyrosinemia Type 1 (HT-1) has greatly improved with early detection through newborn screening and the introduction of nitisinone (NTBC) therapy. A recent guideline calls for periodic monitoring of biochemical markers and NTBC levels to tailor treatment; however, this is currently only achieved through a combination of clinical laboratory tests. We developed a multiplexed assay measuring relevant amino acids, succinylacetone (SUAC), and NTBC in dried blood spots (DBS) to facilitate treatment monitoring. METHODS: Tyrosine, phenylalanine, methionine, NTBC and SUAC were eluted from DBS with methanol containing internal standards for each analyte and analyzed by liquid chromatography tandem mass spectrometry over 6.5 min in the multiple reaction monitoring positive mode. RESULTS: Pre-analytical and analytical factors were studied and demonstrated a reliable assay. Chromatography resolved an unknown substance that falsely elevates SUAC concentrations and was present in all samples. To establish control and disease ranges, the method was applied to DBS collected from controls (n = 284) and affected patients before (n = 2) and after initiation of treatment (n = 29). In the treated patients SUAC concentrations were within the normal range over a wide range of NTBC levels. CONCLUSIONS: This assay enables combined, accurate measurement of revelevant metabolites and NTBC in order to simplify treatment monitoring of patients with HT-1. In addition, the use of DBS allows for specimen collection at home to facilitate more standardization in relation to drug and dietary treatment. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/32546364/Laboratory_monitoring_of_patients_with_hereditary_tyrosinemia_type_I_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(20)30140-2 DB - PRIME DP - Unbound Medicine ER -
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