Serum melatonin kinetics and long-term melatonin treatment for sleep disorders in Rett syndrome.

We studied the circadian rhythm of serum melatonin levels in two patients with classical Rett syndrome having severe sleep disorders; serum melatonin levels were measured before and during melatonin treatment using radioimmunoassay. Patient 1 had a free-running rhythm of sleep-wake cycle from 3 years of age. At the age of 4 years, the peak time of melatonin was delayed 6 h compared to normal control and the peak value was at the lower limit. Patient 2 had a fragmented sleep pattern accompanied by night screaming from 1 year and 6 months of age. At the age of 10 years, the peak time of melatonin secretion was normal but the peak value was at the lower limit. These patients were given 5 mg melatonin orally prior to bedtime. Exogenous melatonin dramatically improved the sleep-wake cycle in patient 1. In patient 2, exogenous melatonin showed a hypnotic effect but early morning awakenings occurred occasionally. When melatonin treatment was stopped, the sleep disorders recurred and re-administration of 3 mg melatonin was effective in both patients. The effect was maintained over 2 years without any adverse effects. These findings suggests that sleep disorders in patients with Rett syndrome may relate with an impaired secretion of melatonin.