Morning specimen is not representative of metabolic control in Tunisian children with phenylketonuria: a repeated cross-sectional study

Objective and methodsTo evaluate variation of capillary phenylalanine concentrations over the day in patients treated for phenylketonuria and the reliability of the morning sample to assess metabolic control, we conducted a repeated cross-sectional study in 25 Tunisian patients on phenylalanine-low diet. For each patient, we collected nine capillary samples over the day. Phenylalanine was dosed by fluorimetry.ResultsThere was a wide variability of phenylalanine concentrations over the day (p<0.001). Compared to morning sample, phenylalanine concentration was significantly lower before lunch (p=0.038), after lunch (p=0.025), before dinner (p<0.001), after dinner (p=0.035) and at 4:00 a.m. (p=0.011). Compared to the 24 h sampling, the morning sample had a 68% to identify unbalanced patients. 60% of patients, had peak phenylalanine concentration after the morning. Half of the patients with normal morning phenylalanine concentration had low phenylalanine values over 8–20 h. Percentages of high phenylalanine concentrations over the last semester were higher in patients with poor metabolic control over the 24 h (21% ± 43 vs. 0% ± 9%); p=0.043.ConclusionA single morning sample gives an incomplete information on metabolic control in phenylketonuric patients. Using four pre-prandial samples on the day should be considered as alternative in patients with good metabolic control.

A phosphoproteomic approach reveals that PKD3 controls phenylalanine and tyrosine metabolism

SummaryMembers of the Protein Kinase D (PKD) family (PKD1, 2, and 3) integrate hormonal and nutritional inputs to regulate complex cellular metabolism. Despite the fact that a number of functions have been annotated to particular PKDs, their molecular targets are relatively poorly explored. PKD3 promotes insulin sensitivity and suppresses lipogenesis in the liver. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified over three-hundred putative targets of PKD3. Among them phenylalanine hydroxylase (PAH). PAH catalyses the conversion of phenylalanine to tyrosine and its activity is regulated by, phenylalanine concentration and glucagon-induced signaling. Consistently, we showed that PKD3 is activated by glucagon and promotes tyrosine levels in primary hepatocytes and liver of mice.Taken together, our comprehensive proteomic approach established that PKD3 determine the rate of phenylalanine to tyrosine conversion in the liver. Therefore, our data indicate that PKD3 might play a role in development of diseases related to the defective tyrosine and phenylalanine metabolism.

Csontanyagcsere felnőtt phenylketonuriás pácienseknél – hazai adatok

Introduction: Patients with phenylketonuria have lower bone mineral density compared to healthy people, however, the ethiology of these alterations is not clear. Hungarian data were missing in this topic. Aim: The main aim of our study was to survey the correlation between metabolic control and change of bone mineral density in early treated Hungarian adult patients with phenylketonuria. Method: In this monocentric study bone mineral density of 59 adult PKU patients have been repeatedly measured in a 4-year interval using dual-energy X-ray absorptiometry. Two subgroups have been established based on average blood phenylalanine levels. The correlation between the change in bone mineral density and average phenylalanine, tyrosine concentrations have been determined while initial bone mineral density and change have also been examined in the subgroups. Results: Mean phenylalanine concentration was 614 (182–1222) micromol/L, whereas mean tyrosine concentration was 49 (24–99) micromol/L and the calculated ratio was 16 (4,5–35). Three patients have had severely decreased bone mineral density in either localisation while 22 have had mild decrease. Low bone mineral density compared to cronological age has been found by 9 patient. The mean change was +0.0380 (–0.1550–0.7800) g/cm2 in femur, and +0.0120 (–0.57300–0.3130) g/cm2 in the lumbar spine. There was a correlation in the change in Z-score neither with mean phenylalanine nor with tyrosine concentration. Conclusions: Bone mineral density was not changed and hardly influenced by the metabolic control in early-treated young adult phenylketonuria patients in a few years interval. Orv Hetil. 2017; 158(47): 1868–1872.