Impaired Melatonin Secretion Disrupts Sleep in Angelman Syndrome Patients, Study Finds

Iqra Mumal, MSc avatar

by Iqra Mumal, MSc |

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The melatonin secretion profile of patients with Angelman syndrome is impaired, leading to a variety of sleep problems, a new study shows.

The study, “Melatonin and Angelman syndrome – implications and mathematical model of diurnal secretion,” was published in the International Journal of Endocrinology.

Sleep disturbances have been known to be severe and frequent in 90 percent of patients with Angelman  syndrome (AS). In fact, sleep problems are noted in the clinical diagnostic criteria for AS.

Sleep problems in AS patients tend to occur between 2 and 6 years of age, with the most frequent problems being getting to sleep and a reduced need for sleep. However, the management for sleep disorders in AS patients is complex because there is little data to determine the correct approach to therapy.

Further, there is no consistent data on the melatonin diurnal (daily) profile, in AS patients. Melatonin is a hormone that regulates sleep and wakefulness.

So, researchers conducted a study to determine the melatonin secretion patterns in children with AS. Since all AS patients in this study had epilepsy, researchers also included children with and without epilepsy to determine which effects were specific to AS.

Researchers constructed a mathematical model of melatonin circadian secretion to determine the hormone secretion pattern. They measured characteristics such as minimum melatonin concentration, release amplitude, phase shift of melatonin release, sleep duration, and dim light melatonin onset (DLMO) of melatonin secretion, an important circadian marker.

Mathematical analysis allowed for modeling of melatonin secretion for each patient. Results showed that 67 percent of AS patients had severely disturbed melatonin secretion.

Furthermore, comparison of variables between the study populations showed that the phase shift of melatonin release was significantly different and sleep duration was significantly longer in the AS group compared to the control group.

Furthermore, dim light melatonin offset (DLMOoff) time, which is when melatonin levels diminish in the morning, was longer in patients with AS compared to epileptic and control patients.

Results indicated that the melatonin secretion is disturbed in a majority of AS patients.

“These results confirm that a variety of sleep problems may exist in a significant portion of individuals with Angelman syndrome, most prominently in the areas of sleep-wake patterns and sleep duration,” the researchers concluded.

One of the limitations of this study is that the effects of medication or drugs on the melatonin cycle were not taken into account.