Sleep Disturbances in Phenylketonuria: An Explorative Study in Men and Mice

Frontiers in Neurology

Francjan J. van Spronsen¹  Anita MacDonald²  Marijke C. M. Gordijn⁴  Eddy A. Van der Zee⁵  Vibeke M. Bruinenberg⁵ 

[1] Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, Netherlands;Birmingham Children’s Hospital, Birmingham, UK;Chrono@work B.V., Groningen, Netherlands;Chronobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, Netherlands;Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, Netherlands;

关键词: inherited metabolic disorder;    Pahenu2 mice;    phenylketonuria patients;    phenylketonuria mice;    neurotransmitters;    sleep disorders;   

DOI  :  10.3389/fneur.2017.00167

来源: DOAJ

【 摘 要 】

Sleep problems have not been directly reported in phenylketonuria (PKU). In PKU, the metabolic pathway of phenylalanine is disrupted, which, among others, causes deficits in the neurotransmitters and sleep modulators dopamine, norepinephrine, and serotonin. Understanding sleep problems in PKU patients may help explain the pathophysiology of brain dysfunction in PKU patients. In this explorative study, we investigated possible sleep problems in adult treated PKU patients and untreated PKU mice. In the PKU patients, sleep characteristics were compared to healthy first degree relatives by assessment of sleep disturbances, sleep–wake patterns, and sleepiness with the help of four questionnaires: Holland sleep disorder questionnaire, Pittsburgh sleep quality index, Epworth sleepiness scale, and Munich Chronotype Questionnaire. The results obtained with the questionnaires show that PKU individuals suffer more from sleep disorders, a reduced sleep quality, and an increased latency to fall asleep and experience more sleepiness during the day. In the PKU mice, activity patterns were recorded with passive infrared recorders. PKU mice switched more often between active and non-active behavior and shifted a part of their resting behavior into the active period, confirming that sleep quality is affected as a consequence of PKU. Together, these results give the first indication that sleep problems are present in PKU. More detailed future research will give a better understanding of these problems, which could ultimately result in the improvement of treatment strategies by including sleep quality as an additional treatment target.

【 授权许可】

Unknown