Newborn screening 50 years later: access issues faced by adults with PKU

Abstract

Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease.Genet Med 2013:15(8):591–599

Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria

“…Populations in most studies were poorly defined and likely heterogeneous. Published studies in adults with PKU necessarily reflect selection bias because a large percentage of adults with PKU are reported as lost to follow-up by metabolic clinics (Berry et al, 2013). The rarity of studies using a rigorous methodology reflects the challenges of recruiting a sufficient numbers of adults with this rare condition who have the requisite effort and ability to maintain a Phe-restricted diet over a sustained amount of time.…”

“…This variability is amplified further by the changes that have occurred in the standards of care for PKU over time, across geographic locations, and during the lifespan. Individuals with PKU report substantial difficulty in maintaining recommended blood Phe levels; Phe levels tend to rise as individuals age (C. S. Brown & Lichter-Konecki, 2016); over 70% of adults do not access regular clinical therapy despite recommendations for treatment for life (Berry et al, 2013).…”

Caracterización fenotípica y molecular de una familia colombiana con fenilcetonuria

“…La principal ruta metabólica de la fenilalanina es su hidroxilación a tirosina por medio de la enzima PAH y el uso de la tetrahidrobiopterina (BH 4 ) como cofactor; esta enzima se reduce después de la reacción y se regenera por medio de la reductasa de dihidropterina (DHPR) (1,2,4,6).…”

“…Su prevalencia en la población caucásica fluctúa entre 1:4.000 y 21.000 recién nacidos, con un promedio de 1:10.000 nacidos vivos, dependiendo de la zona geográfica (1,4). Gracias al establecimiento de programas de tamización neonatal a nivel mundial, el cuadro típico de la fenilcetonuria clásica es poco común, ya que se inicia la restricción en la dieta y la administración de preparados de aminoácidos libres de fenilalanina desde el nacimiento (6,8). Sin embargo, es importante señalar que en Colombia aún no se cuenta con este tipo de programas.…”

Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations

“…Rigorous Phe-restrict diet is the cornerstone of therapeutic PKU management [10,11]. Improved clinical findings are ascribed to dietary therapy in phenylketonuric patients, particularly decreasing aberrant plasma Phe levels [12,13]. Nevertheless, some putative side effects have been associated to this therapy, including zinc, selenium and iron deficiencies [14].…”