The neurological and psychological phenotype of adult patients with early‐treated phenylketonuria: A systematic review

Abstract

Newborn screening for phenylketonuria (PKU) and early introduction of dietary therapy has been remarkably successful in preventing the severe neurological features of PKU, including mental retardation and epilepsy. However, concerns remain that long‐term outcome is still suboptimal, particularly in adult patients who are no longer on strict phenylalanine‐restricted diets. With our systematic literature review we aimed to describe the neurological phenotype of adults with early‐treated phenylketonuria (ETPKU). The literature search covered the period from 1 January 1990 up to 16 April 2018, using the NLM MEDLINE controlled vocabulary. Of the 643 records initially identified, 83 were included in the analysis. The most commonly reported neurological signs were tremor and hyperreflexia. The overall quality of life (QoL) of ETPKU adults was good or comparable to control populations, and there was no evidence for a significant incidence of psychiatric disease or social difficulties. Neuroimaging revealed that brain abnormalities are present in ETPKU adults, but their clinical significance remains unclear. Generally, intelligence quotient (IQ) appears normal but specific deficits in neuropsychological and social functioning were reported in early‐treated adults compared with healthy individuals. However, accurately defining the prevalence of these deficits is complicated by the lack of standardized neuropsychological tests. Future research should employ standardized neurological, neuropsychological, and neuroimaging protocols, and consider other techniques such as advanced imaging analyses and the recently validated PKU‐specific QoL questionnaire, to precisely define the nature of the impairments within the adult ETPKU population and how these relate to metabolic control throughout life.

Determining factors of the cognitive outcome in early treated PKU: A study of 39 pediatric patients

“…Additionally, a notably impaired executive function in ETPKU patients has been well documented [11]. A recent review summarizes neuropsychological findings in ETPKU patients [12]. In response to these findings, recent guidelines recommend life-long Phe-restricted diet and new treatment targets for ETPKU patients [13].…”

The Impact of a Slow-Release Large Neutral Amino Acids Supplement on Treatment Adherence in Adult Patients with Phenylketonuria

“…The second limitation was related to the self-rating instruments, which could be influenced by some bias, such as memory bias, patient education, the complex psychological phenotype of adult PKU patients, and more practical issues, such as the availability of web-based material [ 36 , 37 ].…”

A Microbial Community Ecology Perspective on the Gut-Microbiome-Brain Axis

“…Nevertheless, in many PKU patients with normal cognitive function Phe levels still influence brain performance ( 18 ). Alternatively, it has been shown that inconsistencies in neurocognitive, psychosocial and metabolic consequences of PKU remain, despite treatment ( 19 – 22 ).…”