Noushin Rostampour1,2, Rojin Chegini3, Silva Hovsepian4,5, Farzaneh Zamaneh6, Mahin Hashemipour3,7. 1. Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. rostampour_n@yahoo.com. 2. Department of Pediatrics, School of Medicine, Imam Hossein Children's Hospital, Isfahan University of Medical Sciences, Isfahan, Iran. rostampour_n@yahoo.com. 3. Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. 4. Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. silvahovsepsecret@gmail.com. 5. Imam Hossein Children's Hospital, Isfahan University of Medical Sciences, Isfahan, Iran. silvahovsepsecret@gmail.com. 6. Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran. 7. Department of Pediatrics, School of Medicine, Imam Hossein Children's Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
Abstract
BACKGROUND: This systematic review study aims to evaluate the cognitive function of patients with mild hyperphenylalaninemia (mHPA) without treatment. METHODS: A systematic literature search was done from the 1st of May to the 30th of July in 2021 on published studies. The search strategy was ((hyperphenylalaninemia) OR (phenylketonuria) AND (cognition)). We use PubMed, Scopus, and the Web of Science databases. Studies which reported their findings regarding the cognitive function of patients with mHPA (screening serum phenylalanine > 120 and < 600 μmol/L) were included and reviewed. RESULTS: From initially retrieved 2805 studies, finally, 15 studies (10 on untreated patients with Phe levels below 360 μmol/L, 7 on untreated patients with Phe levels between 360 and 600 μmol/L, four 120-600 μmol/L) were selected. Most of the studies used the Wechsler Intelligence Scale for IQ evaluation, two (2/15) of them used the Stanford-Binet test and two used both tests. Four studies have reported a worse cognitive outcome compared to the control group, and in one study, relative defects in attention and working memory were reported. Other studies have reported normal IQ levels and no significant cognitive defects. CONCLUSION: It is suggested that Phe levels between 120 and 360 μmol/L are generally safe. Some studies showed that untreated patients with higher levels might show some degrees of cognitive impairment. In conclusion, current knowledge is insufficient to state that treatment is not required for HPA patients to preserve their cognitive status, especially in patients with Phe levels of 360-600 μmol/L. Further studies with a larger sample size and standardized cognitive function evaluation tools are needed.
BACKGROUND: This systematic review study aims to evaluate the cognitive function of patients with mild hyperphenylalaninemia (mHPA) without treatment. METHODS: A systematic literature search was done from the 1st of May to the 30th of July in 2021 on published studies. The search strategy was ((hyperphenylalaninemia) OR (phenylketonuria) AND (cognition)). We use PubMed, Scopus, and the Web of Science databases. Studies which reported their findings regarding the cognitive function of patients with mHPA (screening serum phenylalanine > 120 and < 600 μmol/L) were included and reviewed. RESULTS: From initially retrieved 2805 studies, finally, 15 studies (10 on untreated patients with Phe levels below 360 μmol/L, 7 on untreated patients with Phe levels between 360 and 600 μmol/L, four 120-600 μmol/L) were selected. Most of the studies used the Wechsler Intelligence Scale for IQ evaluation, two (2/15) of them used the Stanford-Binet test and two used both tests. Four studies have reported a worse cognitive outcome compared to the control group, and in one study, relative defects in attention and working memory were reported. Other studies have reported normal IQ levels and no significant cognitive defects. CONCLUSION: It is suggested that Phe levels between 120 and 360 μmol/L are generally safe. Some studies showed that untreated patients with higher levels might show some degrees of cognitive impairment. In conclusion, current knowledge is insufficient to state that treatment is not required for HPA patients to preserve their cognitive status, especially in patients with Phe levels of 360-600 μmol/L. Further studies with a larger sample size and standardized cognitive function evaluation tools are needed.
Authors: Alicia Hillert; Yair Anikster; Amaya Belanger-Quintana; Alberto Burlina; Barbara K Burton; Carla Carducci; Ana E Chiesa; John Christodoulou; Maja Đorđević; Lourdes R Desviat; Aviva Eliyahu; Roeland A F Evers; Lena Fajkusova; François Feillet; Pedro E Bonfim-Freitas; Maria Giżewska; Polina Gundorova; Daniela Karall; Katya Kneller; Sergey I Kutsev; Vincenzo Leuzzi; Harvey L Levy; Uta Lichter-Konecki; Ania C Muntau; Fares Namour; Mariusz Oltarzewski; Andrea Paras; Belen Perez; Emil Polak; Alexander V Polyakov; Francesco Porta; Marianne Rohrbach; Sabine Scholl-Bürgi; Norma Spécola; Maja Stojiljković; Nan Shen; Luiz C Santana-da Silva; Anastasia Skouma; Francjan van Spronsen; Vera Stoppioni; Beat Thöny; Friedrich K Trefz; Jerry Vockley; Youngguo Yu; Johannes Zschocke; Georg F Hoffmann; Sven F Garbade; Nenad Blau Journal: Am J Hum Genet Date: 2020-07-14 Impact factor: 11.025
Authors: Peter Burgard; Kurt Ullrich; Diana Ballhausen; Julia B Hennermann; Carla E M Hollak; Mirjam Langeveld; Daniela Karall; Vassiliki Konstantopoulou; Esther M Maier; Frauke Lang; Robin Lachmann; Elaine Murphy; Sven Garbade; Georg F Hoffmann; Stefan Kölker; Martin Lindner; Johannes Zschocke Journal: Lancet Diabetes Endocrinol Date: 2017-09 Impact factor: 32.069