Creatine Levels in Patients with Phenylketonuria and Mild Hyperphenylalaninemia: A Pilot Study.
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ABSTRACT: Background
Creatine (Cr) levels are strongly dependent on diets, including animal-derived proteins. Cr is an important metabolite as it represents a source of stored energy to support physical performance and potentially sustain positive effects such as improving memory or intelligence. This study was planned to assess Cr levels in PKU children adhering to a diet low in phenylalanine (Phe) content and compared with those of children with mild hyperphenylalaninemia (MHP) on a free diet.Methods
This retrospective pilot study analyzed Cr levels from Guthrie cards in 25 PKU and 35 MHP subjects. Anthropomorphic and nutritional data of the study populations were assessed, compared and correlated.Results
Cr levels of PKU subjects were significantly lower than those of MHP subjects and correlated to the low intake of animal proteins. Although no deficiencies in PKU subjects were identified, PKU subjects were found to have a 26-fold higher risk of displaying Cr levels <25° percentile than MHP counterparts.Conclusions
This pilot study suggests that Cr levels might be concerningly low in PKU children adhering to a low-Phe diet. Confirmatory studies are needed in PKU patients of different age groups to assess Cr levels and the potential benefits on physical and intellectual performance of Cr supplementation.
SUBMITTER: Verduci E
PROVIDER: S-EPMC8148514 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Cardiovascular disease (CVD) is a risk factor for cognitive impairment in the elderly. Manifestations of subclinical CVDs can be found in patients with cognitive impairment. The aim of the present study was to test the hypothesis that patients with mild cognitive impairment (MCI) have different magnetic resonance imaging (MRI)-derived regional myocardial motion indices compared with healthy controls. METHODS:Eleven MCI patients (age, 65.5 years ±5.9; range, 55-81 years old) and 11 sex-/age-matched healthy volunteers were enrolled. All of the participants underwent a head MRI and cardiac MRI. Global cortical atrophy (GCA) was graded on the head MRI. The left ventricular ejection fraction (LVEF) and regional strain, strain rate, displacement and velocity were measured on cine images. The GCA scores, global cardiac function and regional myocardial motion indices were compared between MCI patients and healthy controls using the t-test. RESULTS:MCI patients had a higher GCA score than healthy controls (p = 0.048). However, there was no significant difference in LVEF between MCI patients and controls. Compared to healthy controls, MCI patients had a lower peak radial strain (29.1% ± 24.1% vs. 46.4% ± 43.4%, p < 0.001), lower peak diastolic radial strain rate (3.2 ± 2.4 s- 1 vs. 6.0 ± 3.0 s- 1, p < 0.001), lower peak diastolic circumferential strain rate (2.5 ± 2.1 s- 1 vs. 3.2 ± 2.1 s- 1, p = 0.002), lower peak systolic radial displacement (4.2 ± 2.2 mm vs. 5.2 ± 3.3 mm, p = 0.002), lower peak diastolic radial velocity (31 ± 18 mm/s vs. 45 ± 33 mm/s, p < 0.001), and lower peak diastolic circumferential velocity (178 ± 124 degree/s vs. 217 ± 131 degree/s, p = 0.005). CONCLUSION:MRI-derived regional myocardial strain, strain rate and velocity were found to be different between MCI patients and healthy controls. Regional myocardial motion indices have the potential to become novel quantitative imaging biomarkers for representing the risk of neurodegenerative disorders, such as Alzheimer's disease (AD).
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Project description:The standard treatment for phenylketonuria (PKU) is a lifelong low-phenylalanine (Phe) diet, supplemented with Phe-free protein substitutes; however, adult patients often show poor adherence to therapy. Alternative treatment options include the use of large neutral amino acids (LNAA). The aim of this study was to determine the Phe, tyrosine (Tyr), and Phe/Tyr ratio in a cohort of sub-optimally controlled adult patients with classical PKU treated with a new LNAA formulation. Twelve patients received a Phe-restricted diet plus a slow-release LNAA product taken three times per day, at a dose of 1 g/kg body weight (mean 0.8 ± 0.24 g/kg/day), over a 12-month period. The product is in a microgranulated formulation, which incorporates all amino acids and uses sodium alginate as a hydrophilic carrier to prolong its release. This LNAA formulation provides up to 80% of the total protein requirement, with the rest of the protein supplied by natural food. Patients had fortnightly measurements of Phe and Tyr levels over a 12-month period after the introduction of LNAA. All patients completed the 12-month treatment period. Overall, adherence to the new LNAA tablets was very good compared with a previous amino acid mixture, for which taste was a major complaint by patients. Phe levels remained unchanged (p = 0.0522), and Tyr levels increased (p = 0.0195). Consequently, the Phe/Tyr ratio decreased significantly (p < 0.05) in the majority of patients treated. In conclusion, LNAA treatment increases Tyr levels in sub-optimally controlled adult PKU patients, while offering the potential to improve their adherence to treatment.
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Project description:BackgroundChildren with Phenylketonuria (PKU) need a special diet to avoid a variety of physical and psychological complications. The aim of this study was to compare and assess the effects of two interventions on and levels of phenylalanine and micronutrients in children with PKU.MethodsForty-six children with PKU (ages 1-12 years) and their caregivers were randomly assigned to one of two 10-week interventions: a caregiver educational intervention based on the Integrative Model of Behvioral Prediction (IMBP) and supplementary low-protein-modified foods. Outcomes consisted of Children's plasma phenylalanine and micronutrients (i.e., vitamin B12, vitamin D3, and zinc) and hemoglobin levels. To assess the sustainability of outcomes, we also compared the children's phenylalanine level at five-time points including baseline and 10-week, 6 months, 12 months, and 24 months follow-ups. In addition, caregivers of both groups were asked to complete a questionnaire to assess how well the interventions were implemented as well as satisfaction with interventions.ResultsWhile a large percentage of children had phenylalanine levels out of range indicating non-adherence (69.6% and 81% in the educational and food items group, respectively), micronutrient deficiencies were not prevalent in the patient cohort. The levels of phenylalanine in both groups decreased significantly over time. However, conducting a repeated-measures ANOVA to evaluating the change in groups across five-time points, revealed a significant difference between groups (F = 4.68, p = 0.03). That is, the educational intervention was more effective in lowering the children's phenylalanine level. At 24-month follow-up, the percentage of children with a normal range of phenylalanine level in the educational and food items groups increased to 73.9 and 57.1 percent, respectively, from 26 and 38 percent at baseline. There were no significant changes in children's micronutrients level following the interventions, except in the hemoglobin. In this way, at 10-week follow-up, the mean hemoglobin of children in the educational group reduced significantly (P = 0.041). However, there was no significant difference between the two groups. In general, all caregivers completed the process evaluation checklist, the feedback was largely positive.ConclusionsThe results of this study demonstrated that both educational and providing food item interventions resulted in a significant reduction in phenylalanine levels. Empowering caregivers of patients, creating and fortifying social networks, providing favorable social supports, and providing access to special food items may be effective in controlling PKU.Clinical trial registrationIranian Registry of Clinical Trials (IRCT20180506039548N1). Registered 6th Jun 2018, https://www.irct.ir/trial/30977 .
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