Can Untreated Pku Patients Escape From Intellectual Disability? a Systematic Review Publisher Pubmed



Van Vliet D¹ ; Van Wegberg AMJ^{1, 2} ; Ahring K³ ; Bikmultanowski M⁴ ; Blau N⁵ ; Bulut FD⁶ ; Casas K⁷ ; Didycz B⁴ ; Djordjevic M⁸ ; Federico A⁹ ; Feillet F¹⁰ ; Gizewska M¹¹ ; Gramer G¹² ; Hertecant JL¹³ Show All Authors
Source: Orphanet Journal of Rare Diseases Published:2018

Abstract

Background: Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients. Methods: To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ≥1200 μmol/l; and 3) IQ ≥80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers. Results: In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms. Conclusions: Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients. © 2018 The Author(s).