What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

Dam, Esther van; Daly, Anne; Venema-Liefaard, Gineke; Rijn, M. van; Derks, Terry G J; McKiernan, Patrick; Heiner‐Fokkema, M. Rebecca; MacDonald, Anita; Spronsen, Francjan J. van

doi:10.1007/8904_2016_37

Cited by 12 publications

(22 citation statements)

References 27 publications

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“…In addition to high tyrosine concentrations caused by NTBC treatment, phenylalanine concentrations below the lower limit of normal are often found in TT1 patients [11, 13, 89–92]. Although these low phenylalanine concentrations are usually expected to be caused by the phenylalanine/tyrosine-restricted diet, NTBC itself seems to lower plasma phenylalanine concentrations as well [74].…”

Section: Adverse Effects Of Ntbcmentioning

confidence: 99%

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Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

et al. 2019

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Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in tyrosine catabolism. TT1 is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome. This review showed that the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) in 1992 has revolutionized the outcome of TT1 patients, especially when started pre-clinically. If started early, NTBC can prevent liver failure, renal problems, and neurological attacks and decrease the risk for hepatocellular carcinoma. NTBC has been shown to be safe and well tolerated, although the long-term effectiveness of treatment with NTBC needs to be awaited. The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires lifelong dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to. In addition, neurocognitive problems have been reported since the introduction of NTBC, with hypothesized but as yet unproven pathophysiological mechanisms. Further research should be done to investigate the possible relationship between important clinical outcomes and blood concentrations of biochemical parameters such as phenylalanine, tyrosine, succinylacetone, and NTBC, and to develop clear guidelines for treatment and follow-up with reliable measurements. This all in order to ultimately improve the combined NTBC and dietary treatment and limit possible complications such as hepatocellular carcinoma development, neurocognitive problems, and impaired quality of life. Key Points Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) has been found to be generally safe and has clearly improved treatment and outcomes for patients with tyrosinemia type 1.

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Section: Adverse Effects Of Ntbcmentioning

confidence: 99%

“…No uniform consensus guidelines exist, but the usual advice is to keep phenylalanine concentrations within the normal range (38–78 µmol/L) [32, 94]. Because of the expected drop in phenylalanine concentrations in the afternoon, we advised to keep fasting phenylalanine concentrations above 50 µmol/L [92].…”

Section: Adverse Effects Of Ntbcmentioning

confidence: 99%

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

et al. 2019

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“…In addition, blood spots were made by collecting one drop of capillary blood on a filter card by finger puncture (as is done at home). All blood samples from the patient were taken at the same time at the outpatient clinic to ensure minimal differences between the samples due to diurnal variation in concentrations [13][14][15][16]. Blood spot cards were obtained from Sartorius (TFN Grade 179 g/m 2 , Sartorius Stedim, Göttingen, Germany).…”

Section: Methodsmentioning

confidence: 99%

Dried blood spot versus venous blood sampling for phenylalanine and tyrosine

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et al. 2020

Orphanet J Rare Dis

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Background: This study investigated the agreement between various dried blood spot (DBS) and venous blood sample measurements of phenylalanine and tyrosine concentrations in Phenylketonuria (PKU) and Tyrosinemia type 1 (TT1) patients. Study design: Phenylalanine and tyrosine concentrations were studied in 45 PKU/TT1 patients in plasma from venous blood in lithium heparin (LH) and EDTA tubes; venous blood from LH and EDTA tubes on a DBS card; venous blood directly on a DBS card; and capillary blood on a DBS card. Plasma was analyzed with an amino acid analyzer and DBS were analyzed with liquid chromatography-mass spectrometry. Agreement between different methods was assessed using Passing and Bablok fit and Bland Altman analyses. Results: In general, phenylalanine concentrations in LH plasma were comparable to capillary DBS, whereas tyrosine concentrations were slightly higher in LH plasma (constant bias of 6.4 μmol/L). However, in the low phenylalanine range, most samples had higher phenylalanine concentrations in DBS compared to LH plasma. Remarkably, phenylalanine and tyrosine in EDTA plasma were higher compared to all other samples (slopes ranging from 7 to 12%). No differences were observed when comparing capillary DBS to other DBS. Conclusions: Overall agreement between plasma and DBS is good. However, bias is specimen-(LH vs EDTA), and possibly concentration-(low phenylalanine) dependent. Because of the overall good agreement, we recommend the use of a DBS-plasma correction factor for DBS measurement. Each laboratory should determine their own factor dependent on filter card type, extraction and calibration protocols taking the LH plasma values as gold standard.

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“…However, during longer term follow-up, it is challenging to maintain both tyrosine and phenylalanine concentrations within target range. As a consequence, low phenylalanine concentrations are reported frequently [4,9,10,11,12,13]. It has been shown that phenylalanine concentrations tend to show a diurnal variation with lowest concentrations during the afternoon [13].…”

Section: Introductionmentioning

confidence: 99%

“…As a consequence, low phenylalanine concentrations are reported frequently [4,9,10,11,12,13]. It has been shown that phenylalanine concentrations tend to show a diurnal variation with lowest concentrations during the afternoon [13]. Low phenylalanine concentrations are associated with poor growth, eczema-like skin eruptions and developmental delay in infants [11], and behavioral problems later in life [14].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Various Doses of Phenylalanine Supplementation on Blood Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients

et al. 2019

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Tyrosinemia type 1 (TT1) treatment with 2-(2-nitro-4-trifluormethyl-benzyl)-1,3-cyclohexanedione (NTBC) and a phenylalanine-tyrosine restricted diet is associated with low phenylalanine concentrations. Phenylalanine supplementation is prescribed without comprehensive consideration about its effect on metabolic control. We investigated the effect of phenylalanine supplementation on bloodspot phenylalanine, tyrosine, NTBC and succinylacetone. Eleven TT1 patients received 0, 20 and 40 mg/kg/day phenylalanine supplementation with the phenylalanine-tyrosine free L-amino acid supplements. Bloodspots were collected before breakfast, midday and evening meal. Differences between study periods, sample times and days within a study period were studied using (generalized) linear mixed model analyses. Twenty and 40 mg/kg/day phenylalanine supplementation prevented daytime phenylalanine decreases (p = 0.05) and most low phenylalanine concentrations, while tyrosine concentrations increased (p < 0.001). Furthermore, NTBC and succinylacetone concentrations did not differ between study periods. To conclude, 20 mg/kg/day phenylalanine supplementation can prevent most low phenylalanine concentrations without increasing tyrosine to concentrations above the target range or influencing NTBC and succinylacetone concentrations, while 40 mg/kg/day increased tyrosine concentrations to values above the targeted range. Additionally, this study showed that the effect of phenylalanine supplementation, and a possible phenylalanine deficiency, should be assessed using pre-midday meal blood samples that could be combined with an overnight fasted sample when in doubt.

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What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

Cited by 12 publications

References 27 publications

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

Dried blood spot versus venous blood sampling for phenylalanine and tyrosine

The Effect of Various Doses of Phenylalanine Supplementation on Blood Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients

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