Maternal phenylketonuria, PKU, has a detrimental effect on embryogenesis. Infant pathology is independent of fetal genotype, but is directly correlated with excessive phenylalaninaemia throughout pregnancy. Although normal children have been delivered by affected mothers who either had benign hyperphenylalaninaemia or in whom strict diet has apparently maintained maternal phenylalaninaemia in the low normal range from before conception, more abnormal than normal births have been reported. In addition, attempts at dietary management are often unsuccessful; most reported cases documented various severe pathological consequences of maternal PKU. Currently available methods provide viable alternative treatment. In vitro fertilization using the parental gametes, followed by implantation of the pre-embryo in a surrogate mother, would avoid a metabolic environment impairing normal development, and therefore should be recommended as alternative therapy for potential mothers with PKU.
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http://dx.doi.org/10.1007/BF00711511 | DOI Listing |
J Pediatr Endocrinol Metab
January 2025
Department of Rare Diseases, Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Türkiye.
Objectives: Phenylketonuria (PKU) and tyrosinemia type 3 (HT3) are both rare autosomal recessive disorders of phenylalanine-tyrosine metabolism. PKU is caused by a deficiency in phenylalanine hydroxylase (PAH), leading to elevated phenylalanine (Phe) and reduced tyrosine (Tyr) levels. HT3, the rarest form of tyrosinemia, is due to a deficiency in 4-hydroxyphenylpyruvate dioxygenase (HPD).
View Article and Find Full Text PDFLab Chip
January 2025
Hacettepe University, Institute of Science, Nanotechnology and Nanomedicine Division, Ankara, Turkey.
Phenylketonuria (PKU) is characterized by an autosomal recessive mutation in the phenylalanine hydroxylase (PAH) gene. Impaired PAH enzyme activity leads to the accumulation of phenylalanine (Phe) and its metabolites in the bloodstream, which disrupts the central nervous system and causes psychomotor retardation. Early diagnosis of PKU is essential for timely intervention.
View Article and Find Full Text PDFInt J Neonatal Screen
December 2024
Laboratory of Genomic, Epigenetics, Precision and Predictive Medicine, School of Medicine, Mohammed VI University of Sciences and Health, Casablanca 82403, Morocco.
Unlabelled: Newborn screening (NBS) represents an important public health measure for the early detection of specified disorders; such screening can prevent disability and death, not only from metabolic disorders but also from endocrine, hematologic, immune, and cardiac disorders. Screening for critical congenital conditions affecting newborns' health is a great challenge, especially in developing countries such as Morocco, where NBS program infrastructure is lacking. In addition, the consanguinity rate is high in Morocco.
View Article and Find Full Text PDFEur J Pediatr
December 2024
Division of Child Neurology, Department of Paediatrics, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
Unlabelled: Phenylalanine (PA) levels below 360 µmol/L do not require treatment; however, cognitive deficits have been observed in patients with elevated PA levels, necessitating a safe upper limit for treatment and therapeutic objectives. The main purpose of this study is to evaluate the correlation between developmental assessments (Denver Developmental Screening Test-II [DDST-II] and Ankara Developmental Screening Inventory [ADSI]) and electroencephalogram (EEG) findings with blood PA levels and genotypic data in non-phenylketonuria mild Hyperphenylalaninemia (HPA) patients, to re-evaluate their treatment status based on potential adverse outcomes. This study encompassed 40 patients aged 1-5 years diagnosed with HPA and not on treatment, identified through initial blood PA levels, and monitored for a minimum of 1 year on an unrestricted diet.
View Article and Find Full Text PDFSerotonin exerts numerous neurological and physiological actions in the brain and in the periphery. It is generated by two different tryptophan hydroxylase enzymes, TPH1 and TPH2, in the periphery and in the brain, respectively, which are members of the aromatic amino acid hydroxylase (AAAH) family together with phenylalanine hydroxylase (PAH), degrading phenylalanine, and tyrosine hydroxylase (TH), generating dopamine. In this study, we show that the co-chaperone DNAJC12 is downregulated in serotonergic neurons in the brain of mice lacking TPH2 and thereby central serotonin.
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