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Metabolic and catecholamine response to sympathetic stimulation in early-treated adult male patients with phenylketonuria.

ABSTRACT: PURPOSE:Defective function of phenylalanine hydroxylase in phenylketonuria (PKU) results in the accumulation of phenylalanine (Phe) and the reduction of tyrosine (Tyr) in the blood, interfering in the normal development and function of organs and tissues in the body. Tyr is the precursor of catecholamines, secreted in response to stress by the adrenal medulla and paraganglia. The aim of this study was to evaluate plasma catecholamine and amino acid response to an escalating series of sympathetic stress tests in PKU patients. METHODS:Twelve males with classical PKU (aged 18-41 years) and ten healthy male controls were included in this study. The subjects were exposed to three different sympathetic stress stimulations: cold pressor, isometric handgrip, and peak treadmill tests to exhaustion. Physiological, metabolic, and hormonal changes were determined. RESULTS:Aerobic capacity (VO2max) was significantly lower in the PKU group (p?=?0.018); however, relative VO2max was similar in the two groups during the spiroergometric test. No significant differences in norepinephrine or in epinephrine response were found between the two groups during the different stimulation tests. Blood Phe increased significantly in the PKU group compared with controls (p?=?0.027) during the spiroergometric test, while Tyr levels remained stable in both groups. CONCLUSION:PKU itself might not influence stress-induced catecholamine changes. Only strenuous exercise increased blood Phe levels in PKU subjects.

SUBMITTER: Sumanszki C

PROVIDER: S-EPMC7426284 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Metabolic and catecholamine response to sympathetic stimulation in early-treated adult male patients with phenylketonuria.

Sumanszki Csaba C Kovacs Krisztian K Karvaly Gellert Balazs GB Kiss Erika E Simon Erika E Patocs Attila A Toth Miklos M Komka Zsolt Z Reismann Peter P

Hormones (Athens, Greece) 20200128 3

<h4>Purpose</h4>Defective function of phenylalanine hydroxylase in phenylketonuria (PKU) results in the accumulation of phenylalanine (Phe) and the reduction of tyrosine (Tyr) in the blood, interfering in the normal development and function of organs and tissues in the body. Tyr is the precursor of catecholamines, secreted in response to stress by the adrenal medulla and paraganglia. The aim of this study was to evaluate plasma catecholamine and amino acid response to an escalating series of sym ...[more]

PMID: 31993977

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Project description:BackgroundPhenylketonuria (PKU) is an inborn error of metabolism affecting the conversion of phenylalanine (Phe) into tyrosine. Previous research has found cognitive and functional brain alterations in individuals with PKU even if treated early. However, little is known about working memory processing and its association with task performance and metabolic parameters. The aim of the present study was to examine neural correlates of working memory and its association with metabolic parameters in early-treated adults with PKU.MethodsThis cross-sectional study included 20 early-treated adults with PKU (mean age: 31.4 years ± 9.0) and 40 healthy controls with comparable age, sex, and education (mean age: 29.8 years ± 8.2). All participants underwent functional magnetic resonance imaging (fMRI) of working memory to evaluate the fronto-parietal working memory network. Fasting blood samples were collected from the individuals with PKU to acquire a concurrent plasma amino acid profile, and retrospective Phe concentrations were obtained to estimate an index of dietary control.ResultsOn a cognitive level, early-treated adults with PKU displayed significantly lower accuracy but comparable reaction time in the working memory task compared to the control group. Whole-brain analyses did not reveal differences in working memory-related neural activation between the groups. Exploratory region-of-interest (ROI) analyses indicated reduced neural activation in the left and right middle frontal gyri and the right superior frontal gyrus in the PKU group compared to the control group. However, none of the ROI analyses survived correction for multiple comparisons. Neural activation was related to concurrent Phe, tyrosine, and tryptophan concentrations but not to retrospective Phe concentrations.ConclusionIn early-treated adults with PKU, cognitive performance and neural activation are slightly altered, a result that is partly related to metabolic parameters. This study offers a rare insight into the complex interplay between metabolic parameters, neural activation, and cognitive performance in a sample of individuals with PKU.

Project description:BackgroundIn phenylketonuria, dietary treatment prevents most of the severe brain disease. However, patients have to follow a diet restricted in several natural components, what may cause decreased bone density and obesity. Exercise is known to improve both mental functioning and bone density also avoiding obesity, and could optimize aspects of central and peripheral outcome, regardless changes in phenylalanine (Phe) levels. However, the acute effects of exercise on metabolic parameters in phenylketonuria patients are unknown and thereby long-term adaptations are unclear. Therefore, this study aimed to evaluate patients' basal metabolic rate (BMR), and their acute response to an aerobic exercise session on plasma concentrations of Phe, tyrosine (Tyr), and branched-chain amino acids (BCAA), as well as metabolic and hormonal responses.MethodsFive early- and four late diagnosed phenylketonuria patients aged 21 ± 4 years and 17 sex-, age-, and BMI-matched controls were evaluated for BMR, peak oxygen consumption (VO2peak) and plasma amino acid, glucose, lipid profile and hormonal levels. At least one week later, participants performed a 30-min aerobic exercise session (intensities individually calculated using the VO2peak results). Blood samples were collected in fasted state (moment 1, M1) and immediately after a small breakfast, which included the metabolic formula for patients but not for controls, and the exercise session (moment 2, M2).ResultsPhenylketonuria patients and controls showed similar BMR and physical capacities. At M1, patients presented higher Phe concentration and Phe/Tyr ratio; and lower levels of BCAA and total cholesterol than controls. Besides that, poorly controlled patients tended to stay slightly below the prescribed VO2 during exercise. Both patients and controls showed increased levels of total cholesterol and LDL at M2 compared with M1. Only controls showed increased levels of Tyr, lactate, and HDL; and decreased Phe/Tyr ratio and glucose levels at M2 compared to values at M1.ConclusionsAcute aerobic exercise followed by a Phe-restricted breakfast did not change Phe concentrations in treated phenylketonuria patients, but it was associated with decreased Phe/Tyr only in controls. Further studies are necessary to confirm our results in a higher number of patients.

Project description:BackgroundEven though early dietary management of phenylketonuria (PKU) successfully prevents severe neurological impairments, deficits in cognitive functioning are still observed. These deficits are believed to be the result of elevated levels of phenylalanine throughout life. Research on cognitive functioning in adults with PKU (AwPKU) often focuses on domains shown to be compromised in children with PKU, such as attention and executive functions, whereas other cognitive domains have received less attention. This systematic review aimed to provide an overview of cognitive functioning across domains examined in early treated (ET) AwPKU.MethodsA systematic search was performed in Ovid MEDLINE(R), PsycINFO, Web of Science, Cochrane, Scopus, Embase, ScienceDirect, and PubMed for observational studies on cognitive performance in ET AwPKU.ResultsTwenty-two peer-reviewed publications, reporting on outcomes from 16 studies were reviewed. Collectively, the results most consistently showed deficits in vigilance, working memory and motor skills. Deficits in other cognitive domains were less consistently observed or were understudied. Furthermore, despite reports of several associations between cognitive performance and phenylalanine (Phe) levels throughout life the relationship remains unclear. Inconsistencies in findings across studies could be explained by the highly heterogeneous nature of study samples, resulting in large inter- and intra-variability in Phe levels, as well as the use of a variety of tests across cognitive domains, which differ in sensitivity. The long-term cognitive outcomes of early and continuous management of PKU remain unclear.ConclusionsTo better understand the development of cognitive deficits in ET AwPKU, future research would benefit from 1) (inter)national multicentre-studies; 2) more homogeneous study samples; 3) the inclusion of other nutritional measures that might influence cognitive functioning (e.g. Phe fluctuations, Phe:Tyrosine ratio and micronutrients such as vitamin B12); and 4) careful selection of appropriate cognitive tests.

Dataset Information

Metabolic and catecholamine response to sympathetic stimulation in early-treated adult male patients with phenylketonuria.

Publications

Metabolic and catecholamine response to sympathetic stimulation in early-treated adult male patients with phenylketonuria.

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