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Blood phenylalanine instability strongly correlates with anxiety in phenylketonuria.

ABSTRACT: We assessed the relationship between anxiety and long-term metabolic control in adolescents with phenylketonuria (PKU). We used a standardized psychological test to measure anxiety level and analyzed lifelong blood phenylalanine stability in a selected group of 25 PKU teenagers with treatment adherence problems. We demonstrated significant correlations of anxiety with variability of blood phenylalanine concentrations and with severity of hyperphenylalaninemia. Avoiding blood phenylalanine fluctuations in childhood can probably reduce anxiety in PKU adolescents.

SUBMITTER: Didycz B

PROVIDER: S-EPMC5758931 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Blood phenylalanine instability strongly correlates with anxiety in phenylketonuria.

Didycz Bozena B Bik-Multanowski Miroslaw M

Molecular genetics and metabolism reports 20171227

We assessed the relationship between anxiety and long-term metabolic control in adolescents with phenylketonuria (PKU). We used a standardized psychological test to measure anxiety level and analyzed lifelong blood phenylalanine stability in a selected group of 25 PKU teenagers with treatment adherence problems. We demonstrated significant correlations of anxiety with variability of blood phenylalanine concentrations and with severity of hyperphenylalaninemia. Avoiding blood phenylalanine fluctu ...[more]

PMID: 29326880

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Blood phenylalanine reduction reverses gene expression changes observed in a mouse model of phenylketonuria.

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Phenylketonuria: an inborn error of phenylalanine metabolism.

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| S-EPMC2423317 | biostudies-literature

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| S-EPMC7218298 | biostudies-literature

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| S-EPMC3902384 | biostudies-literature

Phenylketonuria: brain phenylalanine concentrations relate inversely to cerebral protein synthesis.

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Mutation analysis of Phenylalanine hydroxylase gene in Iranian patients with Phenylketonuria.

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Project description:Introduction:Phenylketonuria (PKU) is an inborn error of metabolism characterized by pathogenic variants of the phenylalanine hydroxylase (PAH) gene with a resulting accumulation of phenylalanine (Phe) to neurotoxic levels. Diagnosis of PKU in the Latvian population began in 1985 and the present study's aim was to evaluate the available data on all PKU patients in Latvia. Materials and methods:The medical records of 116 - DNA sample was available in 110 patients (102 nonrelated individuals) diagnosed with PKU in Latvia were obtained. Phe concentrations were measured in dried blood spots. Genomic DNA was analyzed for pathogenic variants in the PAH gene. Biochemical data were available through follow-up visits of the 83 patients. Results:In 97% of patients (99 of 102), pathogenic variants were detected on both alleles. With an occurrence of 69.6%%, the most common pathogenic variant was the severe pathogenic variant p.Arg408Trp. The available data for 83 patients revealed that metabolic control was better in younger age groups and worse in adults. Conclusion:Latvia exhibits a relatively homogeneous pool of disease-causing PKU alleles with a high prevalence of the classical severe form of PKU. Dietary compliance in all patients' groups is lower than expected, especially it is poor in adult age group.

| S-EPMC7578541 | biostudies-literature

Long-Term Metabolic Correction of Phenylketonuria by AAV-Delivered Phenylalanine Amino Lyase.

Project description:Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutation within phenylalanine hydroxylase (PAH) gene. Loss-of-function of PAH leads to accumulation of phenylalanine in the blood/body of an untreated patient, which damages the developing brain, causing severe mental retardation. Current gene therapy strategies based on adeno-associated vector (AAV) delivery of PAH gene were effective in male animals but had little long-term effects on blood hyperphenylalaninemia in females. Here, we designed a gene therapy strategy using AAV to deliver a human codon-optimized phenylalanine amino lyase in a liver-specific manner. It was shown that PAL was active in lysing phenylalanine when it was expressed in mammalian cells. We produced a recombinant adeno-associated vector serotype 8 (AAV8) viral vector expressing the humanized PAL under the control of human antitrypsin (hAAT) promoter (AAV8-PAL). A single intravenous administration of AAV8-PAL caused long-term correction of hyperphenylalaninemia in both male and female PKU mice (strain Pahenu2). Besides, no obvious liver injury was observed throughout the treatment process. Thus, our results established that AAV-mediated liver delivery of PAL gene is a promising strategy in the treatment of PKU.

| S-EPMC7733040 | biostudies-literature

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