The outcome of white matter abnormalities in early treated phenylketonuric patients: A retrospective longitudinal long-term study.
BACKGROUND
Pathogenesis and clinical consequences of white matter abnormalities on magnetic resonance imaging (MRI) in phenylketonuric (PKU) patients are incompletely known.


OBJECTIVE
To study white matter alterations progression and outcome and its relationships with phenylalanine levels and intelligence quotient (IQ) in early treated PKU subjects who underwent serial MRIs during a prolonged follow-up.


METHODS
47 early treated PKU patients (mean age 25.1 ± 5.6 years; range 12-37 years) have been enrolled when two or more consecutive brain MRIs, a complete biochemical history, and MRI-concurrent blood phenylalanine levels were available. The severity and extension of white matter abnormalities were expressed in a computed score. Consecutive IQ assessments were available in 24 patients. We analyzed intra- and interindividual white matter alterations variations and their relationship with quality of biochemical control and cognitive outcome.


RESULTS
Early treated PKU patients showed a high rate of white matter alterations with a relevant increase in frequency/severity from the second decade of life onwards. Age and quality of dietary control before or between subsequent examinations showed an independent cumulative effect on white matter alterations outcome. No significant association was found between white matter alterations and cognitive outcome. A remarkable interindividual variability was found and several patients disclosed incongruity between the trajectory of white matter alterations and biochemical control. About 30% of white matter alterations variability remains unexplained by the disease-associated determinants.


CONCLUSIONS
The evolution of white matter alterations is not significantly affected by intellectual outcome and is affected by aging, chronic exposure to phenylalanine, and unknown individual factors.
Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome. Electronic address: mario.mastrangelo@uniroma1.it.
Mario
M
Mastrangelo
Section of NeuroToxicology and Neuroendocrinology, Department of Cell Biology and Neuroscience, National Institute of Health, Rome. Electronic address: flavia.chiarotti@iss.it.
Flavia
F
Chiarotti
Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome. Electronic address: luanaberillo@gmail.com.
Luana
L
Berillo
Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome. Electronic address: caputi.caterina@libero.it.
Caterina
C
Caputi
Department of Experimental Medicine, "Sapienza University of Rome". Electronic address: claudia.carducci@uniroma1.it.
Claudia
C
Carducci
Department of Emergency Radiology, "Sapienza University of Rome"
Claudio
C
Di Biasi
Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome. Electronic address: mantifilippo@libero.it.
Filippo
F
Manti
Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome; Department of Physiology and Pharmacology, "Sapienza University of Rome". Electronic address: francesca.nardecchia@gmail.com.
Francesca
F
Nardecchia
Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome. Electronic address: vincenzo.leuzzi@uniroma1.it.
Vincenzo
V
Leuzzi
D000293:Adolescent; D000328:Adult; D000375:Aging; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007361:Intelligence Tests; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood / Q000473:pathology* / Q000628:therapy*; D012189:Retrospective Studies; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
D010649:Phenylalanine
intellectual outcome in phenylketonuria; intellectual quotient; magnetic resonance; phenylketonuria; white matter outcome in phenylketonuria