Hypersomnia with dilated pupils in adenosine monophosphate deaminase (AMPD) deficiency

Inborn Errors of Purine Salvage and Catabolism

“…A lack of AMPD1, the muscle-specific isoform of AMPD (myoadenylate deaminase deficiency), can cause a metabolic myopathy, with exercise-induced muscle symptoms such as early fatigue, cramps, and/or myalgia [ 185 , 186 , 187 ]. More recently, hypersomnia has also been described [ 188 ]. Although 1–2% of the Caucasian population carries one of the mutations that cause myoadenylate deaminase deficiency, few carriers show symptoms [ 183 ] and the clinical relevance of AMPD1 deficiency has been questioned [ 189 ].…”

“…Based on results from Ampd1 knockout mice, Hafen et al [ 198 ] have suggested that the consequences of AMPD1 deficiency in humans could not be apparent in individuals with a high percentage of slow-twitch fibers (with low AMPD1 expression) or in those with a greater mixed-fiber composition, such as an untrained population [ 198 ]. Hypersomnia could be due to the modulatory effect in the sleep circuits of adenosine, which is able to cross the blood–brain barrier [ 188 ] and may accumulate in AMPD1-deficient individuals as a result of cNs activity on AMP. The increase in adenosine might also be the cause of the protective effect of AMPD1 deficiency on coronary arterial disease and heart failure [ 199 , 200 , 201 ].…”

Possible influence of AMPD1 on cholinergic neurotransmission and sleep

“…Our attention was drawn to this disease by a recent letter in this journal (Perumal et al ., ) reporting a first case of possible impact of AMPD1 deficiency on sleep, accompanied by attenuated pupil constriction and cholinergic super‐sensitivity; the authors hypothesized that these findings could be related to adenosine excess. Recently, we were confronted with another case of AMPD1 deficiency with abnormal sleep and proof of excessive cholinergic tone.…”

“…It is known that adenosine excess due to monophosphate deaminase deficiency (AMPD1) can be linked to muscle problems. Recently, Perumal et al, 2014 reported a first case of possible impact of AMPD1 on sleep, REM sleep and cholinergic neurotransmission. We report a second patient with similar sleep complaints: long sleep duration with residual daytime sleepiness and a need to sleep after exercise.…”