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However, concerns remain that long\u2010term outcome is still suboptimal, particularly in adult patients who are no longer on strict phenylalanine\u2010restricted diets. With our systematic literature review we aimed to describe the neurological phenotype of adults with early\u2010treated 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\u2010treated 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\u2010specific QoL questionnaire, to precisely define the nature of the impairments within the adult ETPKU population and how these relate to metabolic control throughout life.<\/jats:p>","DOI":"10.1002\/jimd.12065","type":"journal-article","created":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T18:29:25Z","timestamp":1548700165000},"page":"209-219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["The neurological and psychological phenotype of adult patients with early\u2010treated phenylketonuria: A systematic review"],"prefix":"10.1002","volume":"42","author":[{"given":"Alessandro P.","family":"Burlina","sequence":"first","affiliation":[{"name":"Neurological Unit St. Bassiano Hospital  Bassano del Grappa 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