Phenylketonuria in adulthood: A collaborative study

Abstract

During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems.

Phenylalanine sensitive K562-D cells for the analysis of the biochemical impact of excess amino acid

“…Depression is one of the common symptoms in adult off-diet PKU patients3334; however, biochemical linkage of the blood phenylalanine level to the depression state has not been resolved. Recent studies in depression have demonstrated that the reduced cerebral protein synthesis, which is also reported in PKU patients with elevated plasma phenylalanine35, is due to low mTORC activity in neuronal cells36.…”

Effect of dietary regime on metabolic control in phenylketonuria: Is exact calculation of phenylalanine intake really necessary?

“…Poor dietary control results in high plasma Phe-concentrations, which lead to neurocognitive impairment and negatively affect attention span, mood [4] and cognitive performance [5]. Consequently, lifelong dietary therapy with good metabolic control is recommended [6].…”

Born at 27 weeks of Gestation with Classical PKU: Challenges of Dietetic Management in a very Preterm Infant

“…In addition, adults with PKU who continued diet performed at a level comparable to genetic expectations as measured by their parents' IQ. 8 High Phe levels are known to be toxic for the fetal brain, as the main consequences of maternal PKU are microcephaly and mental retardation. 9 However, no clear data are available about the effect of high Phe in the brain of premature babies and especially about blood threshold Phe concentrations and/or duration of high Phe levels on clinical outcome of these patients.…”