Laboratory monitoring of patients with hereditary tyrosinemia type I
| Autor: | Rani H. Singh, Matthew J. Schultz, Gisele Pino, Piero Rinaldo, Brian C. Netzel, Kimiyo Raymond, Silvia Tortorelli, Devin Oglesbee, Dietrich Matern, Wendy E. Smith, Dimitar Gavrilov |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Analyte Adolescent Nitisinone Endocrinology Diabetes and Metabolism 030105 genetics & heredity Biochemistry Specimen Handling Young Adult 03 medical and health sciences 0302 clinical medicine Endocrinology Liquid chromatography–mass spectrometry Genetics medicine Humans Amino Acids Child Molecular Biology Aged Aged 80 and over Newborn screening Chromatography Cyclohexanones Tyrosinemias business.industry Selected reaction monitoring Infant Newborn Infant Middle Aged Reference Standards Prognosis Heptanoates Hereditary tyrosinemia Specimen collection Succinylacetone Case-Control Studies Child Preschool Nitrobenzoates Female Laboratories business Biomarkers 030217 neurology & neurosurgery Follow-Up Studies medicine.drug |
| Zdroj: | Molecular Genetics and Metabolism. 130:247-254 |
| ISSN: | 1096-7192 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect