Sleep and Its Disturbance in a Variant Form of Late Infantile Neuronal Ceroid Lipofuscinosis (CLNS)

Abstract

To examine the nature of sleep disturbance in patients with a variant form of late infantile neuronal ceroid lipofuscinosis (CLN5), we studied 12 patients (age range 7-32 years). We used a sleep questionnaire to assess sleep and its disturbances quantitatively. To identify the periodicity in the diurnal rest-activity rhythms, the motor activity level was recorded by activity monitors continuously for a 1-week period with concomitant sleep logs. In addition, whole-night polysomnographic recordings were performed. The patients under 20 years of age had an excess of nocturnal sleep (the mean of the usual duration of nighttime sleep was 10.0 hours) and frequent daytime naps. Frequent shifts of the longest sleep period into the daytime hours and fragmented diurnal rest-activity patterns with no distinct rhythm occurred in the older patients. The progressive disease may damage the internal circadian timing system and also impair the ability of patients with variant late infantile neuronal ceroid lipofuscinosis to use external time cues for synchronization of their sleep and environmental time.

Circadian profiling in two mouse models of lysosomal storage disorders; Niemann Pick type-C and Sandhoff disease

“…Circadian rhythm disruption is frequently observed in neurological disorders and it is becoming apparent that sleep disturbance is a potentially important prodromal symptom in neurodegenerative disease [9] , [10] , [11] ; for example, rapid eye movement sleep behaviour disorder (RBD) is present years before the diagnosis of Parkinson's disease in up to 50% of patients [12] , [13] . Similar observations have been documented in LSDs, including patients with juvenile neuronal ceroid lipofuscinosis and Sanfilippo syndrome, where sleep disruption including irregular sleep/wake patterns are commonly reported [14] , [15] , [16] . With particular relevance this study, sleep disruption has been described as a characteristic of patients with infantile and juvenile GM2 gangliosidosis [17] , [18] .…”

PhenomeXcan: Mapping the genome to the phenome through the transcriptome

“…RAS4B ( P = 1.660 × 10 −19 , locus RCP = 0.63) was linked to a transcriptional network regulated by LHX1 involved in circadian control ( 34 ). CLN5 ( P = 5.248 × 10 −18 , locus RCP = 0.34) mutations are associated with neuronal ceroid lipofuscinosis, which can manifest with sleep-specific dysfunction ( 35 ). FBXL3 ( P = 1.54 × 10 −16 , locus RCP = 0.35) assists with turnover of the CRY protein through direct interaction to regulate circadian rhythms ( 36 ).…”

Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging

“…Caudate atrophy would be expected to exacerbate loss of motor control, as well as to complicate cognitive decline. Thalamic degeneration might contribute to seizure generation and could also cause sleep abnormalities that are common at late stages in Batten disease [ 36 ]. We do not know if sleep abnormalities are present in CLN6 Batten disease sheep, although from the regions that are atrophied we predict that they would be present.…”