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Screening and Diagnostic Tests
Published in Marcello Pagano, Kimberlee Gauvreau, Heather Mattie, Principles of Biostatistics, 2022
Marcello Pagano, Kimberlee Gauvreau, Heather Mattie
The goal of newborn screening (nbs) is the detection of infants who are pre-symptomatic, but who have an increased risk of congenital conditions for which early treatment could prevent intellectual and physical disability, even early death. The procedure includes testing a drop of blood – the heel prick sample – and a hearing screen. Although the program started by testing for a single condition, the metabolic disorder phenylketonuria (pku), the number of conditions and tests continues to grow. The disorders included in newborn screening vary across countries and locales, but most include pku, cystic fibrosis, sickle cell disease, critical congenital heart disease, and hearing loss. The majority of these conditions are very rare.
Preconceptual Health
Published in Michelle Tollefson, Nancy Eriksen, Neha Pathak, Improving Women's Health Across the Lifespan, 2021
Nancy L. Eriksen, Kristi R. VanWinden, John McHugh
Maternal phenylketonuria (PKU), otherwise known as phenylalanine hydroxylase deficiency, is associated with a dose-related embryopathy when maternal phenylalanine levels are elevated in early pregnancy. Fetal effects include growth restriction, microcephaly, facial dysmorphology, cardiac malformations, and intellectual disability in a pattern similar to that of fetal alcohol syndrome.66,67 These risks are eliminated if phenylalanine levels are normalized prior to pregnancy through maternal dietary changes. Women with PKU should begin dietary interventions with a goal of normalizing phenylalanine levels for at least 3 months prior to pregnancy and throughout gestation.68
Nutrition Therapy of Inborn Errors of Metabolism
Published in Fima Lifshitz, Childhood Nutrition, 2020
Kimberlee Michals-Matalon, Reuben Matalon
Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism that occurs in approximately one in 10,000 to 15,000 births in the United States.3 The disease occurs in all ethnic groups but is more common in persons of Northern European background. Foiling was the first in 1934 to identify phenylketones in the urine of patients with PKU.4 Jervis in 1947 identified the defective enzyme as phenylalanine hydroxylase involved in the hydroxylation of phenylalanine to tyrosine as shown in Figure 1.5 Bickel in 1953 documented that restricting the substrate, phenylalanine, in patients with PKU prevented the severe manifestations of the disease.6 The successful treatment led to mandatory newborn screening for this disease in the United States.
When Less is More: Lessons for Expanded Carrier Screening from Newborn Sequencing Research
Published in The American Journal of Bioethics, 2023
Newborn screening programs, found around the world, are generally government-funded, universal, public health undertakings. Most include metabolic screening of several spots of blood taken by pricking each infant’s heel shortly after birth (Therrell et al. 2015). In the 1960s, when the first programs began, infants were screened for phenylketonuria (PKU), an inherited disorder that can cause brain damage and intellectual disability, but if detected early in life can be ameliorated through diet or medication. PKU is often considered a textbook example of a condition that meets the widely accepted Wilson and Jungner public health screening criteria (Wilson and Jungner 1968). These criteria include having evidence for the potential net benefit of screening for a condition rather than waiting for clinical presentation and that effective treatment exists. They also include the practical requirements that programs have the funds, staff, and technology to adopt and roll out the test and to provide the necessary follow-up services.
Preclinical and clinical developments in enzyme-loaded red blood cells: an update
Published in Expert Opinion on Drug Delivery, 2023
Marzia Bianchi, Luigia Rossi, Francesca Pierigè, Sara Biagiotti, Alessandro Bregalda, Filippo Tasini, Mauro Magnani
Phenylketonuria (PKU) is an inborn metabolic disease caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene resulting in increased blood phenylalanine (Phe) concentrations which are neurotoxic and lead to severe intellectual disability, autistic behavior, seizures, and epilepsy [57]. The management of PKU has been extensively covered in the literature and recent reviews highlight emerging therapies, which could improve patient health, compliance, and quality of life [58,59]. Among these, the enzyme replacement therapy based on recombinant phenylalanine ammonia lyase (rAvPAL) from Anabaena variabilis, catalyzing the deamination of Phe to the nontoxic product trans-cinnamate, plays a leading role. Indeed, pegvaliase (Palynziq®, BioMarin Pharmaceutical Inc., USAA), a PEGylated recombinant PAL, has been approved by FDA (2018) and EMA (2019) for treatment of adult patients.
Preclinical developments of enzyme-loaded red blood cells
Published in Expert Opinion on Drug Delivery, 2021
Luigia Rossi, Francesca Pierigè, Alessandro Bregalda, Mauro Magnani
Phenylketonuria (PKU) is the most common hereditary disorder of amino acid metabolism among Caucasians (overall incidence 1:10,000). It is caused by a deficiency in the enzyme phenylalanine hydroxylase (PAH; EC 1.14.16.1) (OMIM*612349) that converts L-phenylalanine (Phe) into L-tyrosine, resulting in the accumulation of neurotoxic levels of Phe and severe mental retardation. Genetic screening identifies newborns with PKU who are then immediately placed on a dietary restriction of Phe intake, thus preventing mental disability. However, some specific deficits in the higher-order cognitive processes and frequent psychopathological symptoms can be observed even in early and continuously treated PKU patients [61,62]. Moreover, a survey of patients with PKU reported that only 23% of adult patients [63] were able to maintain blood Phe within the therapeutic range of 120 to 360 µmol/L.