Urine Biomarkers May Identify Down Syndrome Patients with OSA

A panel of urine biomarkers has been identified that may allow clinicians to easily diagnose Down syndrome patients with obstructive sleep apnea (OSA).

OSA occurs when an individual's airway is restricted or blocked during sleep by some physical feature. Affected individuals may briefly stop and then resume breathing. In addition to disturbing sleep, the reduction in oxygen supply can cause cardiovascular problems - including hypertension and arrhythmias - and metabolic issues. The effects of OSA are exacerbated in those with Down syndrome because of their physical and cognitive differences.

Currently polysomnography (PSG) is the method used to diagnose OSA. This is a comprehensive recording of the biophysiological changes that occur during sleep. The PSG monitors many body functions including brain (EEG), eye movements (EOG), muscle activity or skeletal muscle activation (EMG) and heart rhythm (ECG) during sleep. After the identification of the sleep disorder sleep apnea in the 1970s, the breathing functions respiratory airflow and respiratory effort indicators were added along with peripheral pulse oximetry.

Since the PSG process can be disruptive and disturbing for Downs syndrome patients, investigators at Massachusetts General Hospital compared urinary biomarkers in individuals with Down syndrome with and without OSA to those of age- and sex-matched neurotypical developing healthy controls (HC). They further investigated whether it was possible to predict OSA in individuals with Down syndrome using these biomarkers.

To perform the study, the investigators collected urine samples were from 58 individuals with Down syndrome the night before or the morning after their scheduled overnight polysomnogram or both. Concentrations of 12 neurotransmitters were determined by enzyme-linked immunosorbent assay.

Results revealed differences between the urinary biomarkers of participants with Down syndrome who did and did not have OSA - with a combination of four neurotransmitters most clearly distinguishing between the two groups. In addition, there were significant differences between the biomarker signatures of all participants with Down syndrome and those of the control participants, regardless of the presence or absence of OSA.

"How great would it be if one day soon we could collect a simple urine sample from patients with Down syndrome and predict whether or not they might have apnea," said senior author Dr. Brian Skotko, co-director of the Down syndrome program at Massachusetts General Hospital and assistant professor of pediatrics at Harvard Medical School. "It would be such a low-cost way of screening for apnea, that would save many patients and their families the hassle and discomfort of an overnight sleep study."

Dr. Skotko stressed that the results of this study required confirmation in larger groups before biomarker screening can be used to screen for the presence of OSA. "Our findings are not yet ready for prime time," said Dr. Skotko. "Before they can be used in clinical practice, we will need to validate these findings in a new group of patients with Down syndrome, which we are working on right now."

The study was published in the March 7, 2017, online edition of the journal Sleep Medicine.