Kienstra, N.S. (Nienke Sanne) (2017) NTBC concentrations and succinylacetone synthesis in Tyrosinemia type 1 patients treated with phenylalanine supplementation. thesis, Medicine.
Full text available on request.Abstract
BACKGROUND: In Hereditary Tyrosinemia type 1 (HT1), outcome greatly improved since NTBC was introduced. However, dosing, variation during the day and target blood NTBC concentrations, leading to the absence of toxic products (SA), are still less well known. Giving phenylalanine is considered to be important to prevent from too low phenylalanine concentrations. Apart from the fact that this is a very rare disease so that comparing data in large cohorts is quite difficult, it is unclear whether giving phenylalanine supplementation does not cause a change of the effect of NTBC on SA synthesis. AIMS: Therefore, the aims of this study were to investigate the influence of phenylalanine supplementation, on tyrosine concentrations, and by that on NTBC and SA concentrations in blood. METHODS: 4 patients were included, all patients received NTBC twice daily. Blood spots for analysis of phenylalanine, tyrosine, NTBC and SA were collected three times a day for a couple of consecutive days in three different study periods with different phenylalanine dosing regimens. Mean tyrosine and NTBC levels and the number of samples with detectable SA ≥ 0.1 μmol/L were calculated. Statistical analyses were performed, using Friedman test, Wilcoxon Signed Ranks test and Pearson and Spearman correlation tests. RESULTS: Since only four patients could be included in the study, results were mainly needed to be discussed descriptively. Although NTBC intake did not differ, NTBC concentrations in blood seemed to differ between the patients. NTBC did not vary during the day in any of the study periods (p=0.779). Detectable SA was found in 31 (out of 120) samples, the presence of SA did not differ under the different treatment regimens of phenylalanine (p=0.821). The SA samples mainly derived from two patients, one of these patients showed increased tyrosine levels in all study periods together with clear higher NTBC concentrations compared to the other patients. Mean tyrosine levels and percentage of samples with SA per study period tended to show a positive correlation (ρ=0.528, p= 0.078). CONCLUSION: No influence of phenylalanine on the variation of NTBC during the day could be observed. When patient 3 was excluded, due to the fact that his data did not reflect a normal situation, no SA was found when the NTBC concentration in individual samples was above 42.8 μmol/L. Although in general tyrosine is not considered to influence the effectiveness of NTBC, the data of this study suggest that at least that tyrosine levels could affect the effectiveness of NTBC in preventing the synthesis of SA. By that, it seems advisable to prevent from too high tyrosine levels in blood (< 400 μmol/L) .
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisor: and Spronsen, Francjan van and Daily mentor: and Ginkel, Wiggert van and Universitair Medical Centrum Groningen and Metabolic diseases |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:02 |
| Last Modified: | 25 Jun 2020 11:02 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2231 |
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