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Sensors (Basel, Switzerland) Apr 2020Phenylalanine is an amino acid found in breast milk and in many foods, being an essential nutrient. This amino acid is very important for the human body because it is... (Review)
Review
Phenylalanine is an amino acid found in breast milk and in many foods, being an essential nutrient. This amino acid is very important for the human body because it is transformed into tyrosine and, subsequently, into catecholamine neurotransmitters. However, there are individuals who were born with a genetic disorder called phenylketonuria. The accumulation of phenylalanine and of some metabolites in the body is dangerous and may cause convulsions, brain damage and mental retardation. Determining the concentration of phenylalanine in different biologic fluids is very important because it can provide information about the health status of the individuals envisaged. Since such determinations may be made by using electrochemical sensors and biosensors, numerous researchers have developed such sensors for phenylalanine detection and different sensitive materials were used in order to improve the selectivity, sensitivity and detection limit. The present review aims at presenting the design and performance of some electrochemical bio (sensors) traditionally used for phenylalanine detection as reported in a series of relevant scientific papers published in the last decade.
Topics: Biosensing Techniques; Electrochemical Techniques; Equipment Design; Humans; Phenylalanine; Phenylketonurias
PubMed: 32354070
DOI: 10.3390/s20092496 -
American Journal of Human Genetics Dec 2023The c.1222C>T (p.Arg408Trp) variant in the phenylalanine hydroxylase gene (PAH) is the most frequent cause of phenylketonuria (PKU), the most common inborn error of...
The c.1222C>T (p.Arg408Trp) variant in the phenylalanine hydroxylase gene (PAH) is the most frequent cause of phenylketonuria (PKU), the most common inborn error of metabolism. This autosomal-recessive disorder is characterized by accumulation of blood phenylalanine (Phe) to neurotoxic levels. Using real-world data, we observed that despite dietary and medical interventions, most PKU individuals harboring at least one c.1222C>T variant experience chronic, severe Phe elevations and do not comply with Phe monitoring guidelines. Motivated by these findings, we generated an edited c.1222C>T hepatocyte cell line and humanized c.1222C>T mouse models, with which we demonstrated efficient in vitro and in vivo correction of the variant with prime editing. Delivery via adeno-associated viral (AAV) vectors reproducibly achieved complete normalization of blood Phe levels in PKU mice, with up to 52% whole-liver corrective PAH editing. These studies validate a strategy involving prime editing as a potential treatment for a large proportion of individuals with PKU.
Topics: Mice; Animals; Phenylketonurias; Phenylalanine Hydroxylase; Disease Models, Animal; Phenylalanine; Gene Editing
PubMed: 37924808
DOI: 10.1016/j.ajhg.2023.10.005 -
Human Genomics Jul 2022Phenylketonuria (PKU) is a common, autosomal recessive inborn error of metabolism caused by PAH gene variants. After routine genetic analysis methods were applied,...
BACKGROUND
Phenylketonuria (PKU) is a common, autosomal recessive inborn error of metabolism caused by PAH gene variants. After routine genetic analysis methods were applied, approximately 5% of PKU patients were still not diagnosed with a definite genotype.
METHODS
In this study, for the first time, we identified PKU patients with unknown genotypes via single-gene full-length sequencing.
RESULTS
The detection rate of PKU genotype increased from 94.6 to 99.4%, an increase of approximately 5%. The variants c.1199 + 502A > T and 1065 + 241C > A were found at a high frequency in Chinese PKU patients.
CONCLUSION
Our study suggest that single-gene full-length sequencing is a rapid, efficient and cost-effective tool to improve the genotype detection rate of PKU patients. Moreover, we provides additional case data to support pathogenicity of deep intronic variants in PAH.
Topics: Genetic Association Studies; Genotype; Humans; Mutation; Phenylalanine Hydroxylase; Phenylketonurias
PubMed: 35869558
DOI: 10.1186/s40246-022-00397-w -
Developmental Neuropsychology 2016This systematic review and meta-analysis (MA) investigates the impact of elevated blood phenylalanine (Phe) on neuropsychiatric symptoms in adults with phenylketonuria... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis (MA) investigates the impact of elevated blood phenylalanine (Phe) on neuropsychiatric symptoms in adults with phenylketonuria (PKU). The meta-analysis of PKU is challenging because high-quality evidence is lacking due to the limited number of affected individuals and few placebo-controlled, double-blind studies of adults with high and low blood Phe. Neuropsychiatric symptoms associated with PKU exceed general population estimates for inattention, hyperactivity, depression, and anxiety. High Phe is associated with an increased prevalence of neuropsychiatric symptoms and executive functioning deficits whereas low Phe is associated with improved neurological performance. Findings support lifelong maintenance of low blood Phe.
Topics: Adolescent; Adult; Executive Function; Humans; Mental Disorders; Phenylalanine; Phenylketonurias; Young Adult
PubMed: 27805419
DOI: 10.1080/87565641.2016.1243109 -
Journal of Medical Case Reports Nov 2023Phenylketonuria (PKU) is an autosomal recessive disease that belongs to a group of disorders resulting from inborn errors of protein metabolism. It was the first disease...
BACKGROUND
Phenylketonuria (PKU) is an autosomal recessive disease that belongs to a group of disorders resulting from inborn errors of protein metabolism. It was the first disease included in neonatal screening. Neonatal screening has allowed an early diagnosis and treatment of the disease. As a result, an increasing number of women diagnosed with phenylketonuria have reached the reproductive phase of life in good health, and management of pregnancy in women with PKU is becoming more frequent.
CASE PRESENTATION
In this study, we report the case of a 28-year-old Caucasian patient being followed up for phenylketonuria at Ramón y Cajal Hospital's Metabolic Diseases Unit. We describe the patient's gestation, impacted by her and her partner's diagnosis of PKU, classic and mild phenotypes, respectively, resulting in the fetus affectation.
CONCLUSIONS
The description of PKU management-diagnosis, follow-up, and treatment-for both that of patient and that of the gestation with fetus affectation covers a wide sample scenario that shows the effectiveness of pregnancy planning and monitoring of females with PKU and questions the need to carry out a genetic study of gene PKU in the study of fertility.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Adult; Phenylketonurias; Neonatal Screening
PubMed: 37941064
DOI: 10.1186/s13256-023-04209-0 -
Journal of Neurology Aug 2023Phenylketonuria (PKU) is a rare inherited metabolic disorder characterised by elevated phenylalanine (Phe) concentrations that can exert neurotoxic effects if untreated... (Review)
Review
OBJECTIVE
Phenylketonuria (PKU) is a rare inherited metabolic disorder characterised by elevated phenylalanine (Phe) concentrations that can exert neurotoxic effects if untreated or upon treatment discontinuation. This systematic review supported by expert opinion aims to raise awareness among the neurological community on neurological complications experienced by adults with PKU (AwPKU).
METHODS
The PubMed database was searched for articles on neurological signs and symptoms in AwPKU published before March 2022. In addition, two virtual advisory boards were held with a panel of seven neurologists and two metabolic physicians from Germany and Austria. Findings are supported by three illustrative patient cases.
RESULTS
Thirty-nine articles were included. Despite early diagnosis and treatment, neurological signs and symptoms (e.g. ataxia, brisk tendon reflexes, tremor, visual impairment) can emerge in adulthood, especially if treatment has been discontinued after childhood. In PKU, late-onset neurological deficits often co-occur with cognitive impairment and psychiatric symptoms, all of which can be completely or partially reversed through resumption of treatment.
CONCLUSION
Ideally, neurologists should be part of the PKU multidisciplinary team, either to bring lost to follow-up patients back to clinic or to manage symptoms in referred patients, considering that symptoms are often reversible upon regaining metabolic control. The current findings have been combined in a leaflet that will be disseminated among neurologists in Germany and Austria to create awareness.
Topics: Humans; Adult; Child; Diagnosis, Differential; Expert Testimony; Phenylketonurias; Nervous System Diseases; Tremor
PubMed: 37081197
DOI: 10.1007/s00415-023-11703-4 -
Molecular Genetics and Metabolism Dec 2013Fluctuations in blood phenylalanine concentrations may be an important determinant of intellectual outcome in patients with early and continuously treated... (Review)
Review
Fluctuations in blood phenylalanine concentrations may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). This review evaluates the studies on phenylalanine fluctuations, factors affecting fluctuations, and if stabilizing phenylalanine concentrations affects outcomes, particularly neurocognitive outcome. Electronic literature searches of Embase and PubMed were performed for English-language publications, and the bibliographies of identified publications were also searched. In patients with PKU, phenylalanine concentrations are highest in the morning. Factors that can affect phenylalanine fluctuations include age, diet, timing and dosing of protein substitute and energy intake, dietary adherence, phenylalanine hydroxylase genotype, changes in dietary phenylalanine intake and protein metabolism, illness, and growth rate. Even distribution of phenylalanine-free protein substitute intake throughout 24h may reduce blood phenylalanine fluctuations. Patients responsive to and treated with 6R-tetrahydrobiopterin seem to have less fluctuation in their blood phenylalanine concentrations than controls. An increase in blood phenylalanine concentration may result in increased brain and cerebrospinal fluid phenylalanine concentrations within hours. Although some evidence suggests that stabilization of blood phenylalanine concentrations may have benefits in patients with PKU, more studies are needed to distinguish the effects of blood phenylalanine fluctuations from those of poor metabolic control.
Topics: Adult; Age Factors; Biopterins; Diet; Humans; Phenylalanine; Phenylalanine Hydroxylase; Phenylketonurias; PubMed
PubMed: 24090706
DOI: 10.1016/j.ymgme.2013.09.001 -
Canadian Medical Association Journal Jan 1968
Topics: Diet Therapy; Female; Humans; Infant; Infant, Newborn; Male; Phenylketonurias
PubMed: 5635022
DOI: No ID Found -
Canadian Medical Association Journal Oct 1967
Topics: Diet Therapy; Humans; Infant; Phenylketonurias
PubMed: 6052906
DOI: No ID Found -
British Medical Journal Nov 1970
Topics: Female; Humans; Mass Screening; Phenylketonurias; Pregnancy; Pregnancy Complications
PubMed: 5481526
DOI: 10.1136/bmj.4.5732.431