Altered DNA methylation in PAH deficient phenylketonuria

Dobrowolski, Steven F.; Lyons‐Weiler, James; Spridik, Kayla; Biery, Amy; Breck, Jane; Vockley, Jerry; Yatsenko, Svetlana A.; Sultana, Tamanna

doi:10.1016/j.ymgme.2015.04.002

Cited by 22 publications

(12 citation statements)

References 41 publications

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“…Andrade et al found altered methylation capacity resulting in low homocysteine concentrations in 42 subjects with PKU compared to 40 controls, which they attribute to high intakes of folic acid and vitamin B-12 from low-Phe medical food products [ 40 ]. Dobrowolski et al reported methylome repatterning in the brain demonstrated by aberrant DNA methylation in brain tissue of subjects and mice with PKU [ 41 , 42 ]. Given the role of folate in one-carbon metabolism, it is possible that excessive intake of folic acid from both AA-MF and GMP-MF and excessive intake of sulfur-containing amino acids from AA-MF could contribute to gene dysregulation in the brain secondary to aberrant DNA methylation [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Dobrowolski et al reported methylome repatterning in the brain demonstrated by aberrant DNA methylation in brain tissue of subjects and mice with PKU [ 41 , 42 ]. Given the role of folate in one-carbon metabolism, it is possible that excessive intake of folic acid from both AA-MF and GMP-MF and excessive intake of sulfur-containing amino acids from AA-MF could contribute to gene dysregulation in the brain secondary to aberrant DNA methylation [ 41 , 42 ]. In short, excessive folic acid intake from medical foods might contribute to the neuropathology of PKU.…”

Section: Discussionmentioning

confidence: 99%

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Metabolomic Insights into the Nutritional Status of Adults and Adolescents with Phenylketonuria Consuming a Low-Phenylalanine Diet in Combination with Amino Acid and Glycomacropeptide Medical Foods

Stroup

Ney

Murali

et al. 2017

Journal of Nutrition and Metabolism

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Background Nutrient status in phenylketonuria (PKU) requires surveillance due to the restrictive low-Phe diet in combination with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF). Micronutrient profiles of medical foods are diverse, and optimal micronutrient supplementation in PKU has not been established. Methods In a crossover design, 30 participants with PKU were randomized to consume AA-MF and Glytactin™ GMP-MF in combination with a low-Phe diet for 3 weeks each. Fasting venipunctures, medical food logs, and 3-day food records were obtained. Metabolomic analyses were completed in plasma and urine by Metabolon, Inc. Results The low-Phe diets in combination with AA-MF and GMP-MF were generally adequate based on Dietary Reference Intakes, clinical measures, and metabolomics. Without micronutrient supplementation of medical foods, >70% of participants would have inadequate intakes for 11 micronutrients. Despite micronutrient supplementation of medical foods, inadequate intakes of potassium in 93% of participants and choline in >40% and excessive intakes of sodium in >63% of participants and folic acid in >27% were observed. Sugar intake was excessive and provided 27% of energy. Conclusions Nutrient status was similar with AA-MF and Glytactin GMP-MF. More research related to micronutrient supplementation of medical foods for the management of PKU is needed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metabolomic Insights into the Nutritional Status of Adults and Adolescents with Phenylketonuria Consuming a Low-Phenylalanine Diet in Combination with Amino Acid and Glycomacropeptide Medical Foods

Stroup

Ney

Murali

et al. 2017

Journal of Nutrition and Metabolism

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“…Aberrant pattern of DNA methylation has been identified in the postmortem brain of PKU patients (Dobrowolski et al, 2015).…”

Section: Cn S Demyelinati On In Pkumentioning

confidence: 99%

White matter disturbances in phenylketonuria: Possible underlying mechanisms

Ferreira

Rodrigues

Streck

et al. 2020

J of Neuroscience Research

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White matter pathologies, as well as intellectual disability, microcephaly, and other central nervous system injuries, are clinical traits commonly ascribed to classic phenylketonuria (PKU). PKU is an inherited metabolic disease elicited by the deficiency of phenylalanine hydroxylase. Accumulation of l‐phenylalanine (Phe) and its metabolites is found in tissues and body fluids in phenylketonuric patients. In order to mitigate the clinical findings, rigorous dietary Phe restriction constitutes the core of therapeutic management in PKU. Myelination is the process whereby the oligodendrocytes wrap myelin sheaths around the axons, supporting the conduction of action potentials. White matter injuries are implicated in the brain damage related to PKU, especially in untreated or poorly treated patients. The present review summarizes evidence toward putative mechanisms driving the white matter pathology in PKU patients.

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“…Phenylketonuria (PKU) is a faulty metabolism of phenylalanine amino acid, caused by defective action of an enzyme phenylalanine hydroxylase (PAH) [1][2][3]. The phenylalanine is a necessary part of the human diet and is naturally present in all kinds of dietary protein [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…There is no doubt that PKU should be diagnosed in early stages and treated from the very first days of life. Accordingly, it could be as a first inborn errors of metabolism to be screened [1, 3, 4, 7].…”

Section: Introductionmentioning

confidence: 99%

Nano‐biosensor based on reduced graphene oxide and gold nanoparticles, for detection of phenylketonuria‐associated DNA mutation

Seifati

Nasirizadeh²,

Azimzadeh

2018

IET nanobiotechnol.

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Phenylketonuria (PKU)-associated DNA mutation in newborn children can be harmful to his health and early detection is the best way to inhibit consequences. A novel electrochemical nano-biosensor was developed for PKU detection, based on signal amplification using nanomaterials, e.g. gold nanoparticles (AuNPs) decorated on the reduced graphene oxide sheet on the screen-printed carbon electrode. The fabrication steps were checked by field emission scanning electron microscope imaging as well as cyclic voltammetry analysis. The specific alkanethiol single-stranded DNA probes were attached by self-assembly methodology on the AuNPs surface and Oracet blue was used as an intercalating electrochemical label. The results showed the detection limit of 21.3 fM and the dynamic range of 80-1200 fM. Moreover, the selectivity results represented a great specificity of the nano-biosensor for its specific target DNA oligo versus other non-specific sequences. The real sample simulation was performed successfully with almost no difference than a synthetic buffer solution environment.

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Altered DNA methylation in PAH deficient phenylketonuria

Cited by 22 publications

References 41 publications

Metabolomic Insights into the Nutritional Status of Adults and Adolescents with Phenylketonuria Consuming a Low-Phenylalanine Diet in Combination with Amino Acid and Glycomacropeptide Medical Foods

Metabolomic Insights into the Nutritional Status of Adults and Adolescents with Phenylketonuria Consuming a Low-Phenylalanine Diet in Combination with Amino Acid and Glycomacropeptide Medical Foods

White matter disturbances in phenylketonuria: Possible underlying mechanisms

Nano‐biosensor based on reduced graphene oxide and gold nanoparticles, for detection of phenylketonuria‐associated DNA mutation

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