Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria

Veyrat-Durebex, Charlotte; Debeissat, Christelle; Blasco, Hélène; Patin, Franck; Henique, Hélène; Emond, Patrick; Antar, Catherine; Gissot, Valérie; Hérault, Olivier; Maillot, F.

doi:10.1007/8904_2017_16

Cited by 9 publications

(10 citation statements)

References 57 publications

(74 reference statements)

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“…The included studies were published from 1994 [38] to 2023 [39], and their characteristics are detailed in Table 1. Four studies were conducted in Greece [25,27,40,41], three in Turkey [31,42,43], three in Spain [32,44,45], two in Austria [26,46], two in Chile [39,47], two in Japan [29,30], two in the United Kingdom [48,49], two in the USA [38,50], and one each in Germany [51], France [52], Poland [28], and Switzerland [53]. All studies, except for one case-control study [26], were cross-sectional and compared individuals with PKU to healthy controls.…”

Section: Study Characteristicsmentioning

confidence: 99%

Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis

Bokayeva,

Jamka,

Walkowiak

et al. 2024

IJMS

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The published data on the vitamin status of patients with phenylketonuria (PKU) is contradictory; therefore, this systematic review and meta-analysis evaluated the vitamin status of PKU patients. A comprehensive search of multiple databases (PubMed, Web of Sciences, Cochrane, and Scopus) was finished in March 2024. The included studies compared vitamin levels between individuals diagnosed with early-treated PKU and healthy controls while excluding pregnant and lactating women, untreated PKU or hyperphenylalaninemia cases, control groups receiving vitamin supplementation, PKU patients receiving tetrahydrobiopterin or pegvaliase, and conference abstracts. The risk of bias in the included studies was assessed by the Newcastle–Ottawa scale. The effect sizes were expressed as standardised mean differences. The calculation of effect sizes with 95% CI using fixed-effects models and random-effects models was performed. A p-value < 0.05 was considered statistically significant. The study protocol was registered in the PROSPERO database (CRD42024519589). Out of the initially identified 11,086 articles, 24 met the criteria. The total number of participants comprised 770 individuals with PKU and 2387 healthy controls. The meta-analyses of cross-sectional and case–control studies were conducted for vitamin B12, D, A, E, B6 and folate levels. PKU patients demonstrated significantly higher folate levels (random-effects model, SMD: 1.378, 95% CI: 0.436, 2.320, p = 0.004) and 1,25-dihydroxyvitamin D concentrations (random-effects model, SMD: 2.059, 95% CI: 0.250, 3.868, p = 0.026) compared to the controls. There were no significant differences in vitamin A, E, B6, B12 or 25-dihydroxyvitamin D levels. The main limitations of the evidence include a limited number of studies and their heterogeneity and variability in patients’ compliance. Our findings suggest that individuals with PKU under nutritional guidance can achieve a vitamin status comparable to that of healthy subjects. Our study provides valuable insights into the nutritional status of PKU patients, but further research is required to confirm these findings and explore additional factors influencing vitamin status in PKU.

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Section: Study Characteristicsmentioning

confidence: 99%

Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis

Bokayeva,

Jamka,

Walkowiak

et al. 2024

IJMS

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“…100 **evidence for this came from a single cross-sectional study 98 and, therefore, observed deficits in cognitive performance may be due to individual differences and do not necessarily reflect the trajectory of cognitive ageing in PKU. 82 increased ROS production 51,83,84 inhibition of antioxidant enzymes 51,85 reduced gray matter volume [86][87][88][89] • Decreased Tyr and Trp r and other LNAA 1 decreased dopamine and norepinephrine (Tyr) and serotonin (Trp) 1 disruptions in protein synthesis 90…”

Section: Gastrointestinal Pathologymentioning

confidence: 99%

Phenylketonuria, co‐morbidity, and ageing: A review

Vardy

MacDonald

Ford³

et al. 2020

J of Inher Metab Disea

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Phenylketonuria (PKU) is a metabolic condition which, left untreated, results in severe and irreversible brain damage. Newborn screening and the development of the low phenylalanine (Phe) diet have transformed the outcomes for people with PKU. Those who have benefited from early treatment are now approaching their fifth and sixth decade. It is therefore timely to consider multi‐morbidity in PKU and the effects of ageing, in parallel with the wider benefits of emerging treatment options in addition to dietary relaxation. We have conducted the first literature review of co‐morbidity and ageing in the context of PKU. Avenues explored have emerged from limited study of multi‐morbidity to date and the knowledge and critical enquiry of the authors. Findings suggest PKU to have a wider impact than brain development, and result in several intriguing questions that require investigation to attain the best outcomes for people with PKU in adulthood moving through to older age. We recognise the difficulty in studying longitudinal outcomes in rare diseases and emphasise the necessity to develop PKU registries and cohorts that facilitate well‐designed studies to answer some of the questions raised in this review. Whilst awaiting new information in these areas we propose that clinicians engage with patients to make personalised and well‐informed decisions around Phe control and assessment for co‐morbidity.

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“…El glutatión tiene funciones de detoxificación y sirve como almacenamiento y transporte de cisteína, es esencial para la proliferación celular y tiene un papel importante en la apoptosis, ya que la disminución de la cantidad de glutatión es permisiva para la activación de caspasas y la progresión de los mecanismos de apoptosis, en el cerebro se comporta como neurohormona y se ha observado que la deficiencia del mismo está asociada a menor sobrevida de neuronas dopaminérgicas (31). En cuanto a otras defensas antioxidantes no enzimáticas, se ha observado disminución en los niveles de selenio, alfa tocoferol y ácido úrico (32,33). Otra causa de daño significativo en los tejidos es la disminución de ubiquinona-10 debido a que la fenilalanina puede inhibir la acción de la enzima 3-hidroxi-3-metilglutaril-CoA reductasa encargada no solo de la síntesis de colesterol sino también de ubiquinona-10 antioxidante lipofílico que previene la peroxidación de lípidos y desempeña un papel clave en la protección de las membranas biológicas, además ayuda a reciclar un antioxidante natural: la vitamina E (34)(35)(36).…”

Section: Estrés Oxidativounclassified

Deficiencia de fenilalanina hidroxilasa : espectro clínico y estado actual del diagnóstico en Colombia.

et al. 2018

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Las mutaciones del gen PAH generan deficiencia de la enzima fenilalanina hidroxilasa. Su actividad final varía desde una actividad casi nula o indetectable en la fenilcetonuria clásica hasta una actividad residual del 10 al 35% de la normal. Esta alteración corresponde al error innato del metabolismo de los aminoácidos más frecuente, afectando a 1 de cada 10.000 personas. Las diferentes cantidades de fenilalanina en sangre se traducen en un espectro amplio de manifestaciones clínicas que incluyen retraso global del desarrollo, discapacidad intelectual, convulsiones, rasgos autistas y comportamiento agresivo en los casos más graves. El diagnóstico temprano a través de los programas de tamizaje neonatal se considera prioritario pues las intervenciones oportunas evitan el daño del sistema nervioso central. Conclusiones: El diagnóstico en Colombia es tardío, las intervenciones realizadas a partir de ese momento son fútiles pues el deterioro cognitivo es irreparable, por lo tanto es imperativa la realización de pruebas diagnósticas tempranas cuando aún las intervenciones médicas pueden impactar la mejoría clínica del paciente con disminución importante de la morbilidad propia de esta patología, convirtiéndose en una necesidad la ampliación del programa de tamizaje neonatal, el cual estaría amparado bajo la ley colombiana de enfermedades huérfanas.

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Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria

Cited by 9 publications

References 57 publications

Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis

Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis

Phenylketonuria, co‐morbidity, and ageing: A review

Deficiencia de fenilalanina hidroxilasa : espectro clínico y estado actual del diagnóstico en Colombia.

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