Actigraphic investigation of circadian rhythm functioning and activity levels in children with mucopolysaccharidosis type III (Sanfilippo syndrome).

BACKGROUND: Sleep disturbance is part of the behavioural phenotype of the rare genetic condition mucopolysaccharidosis (MPS) type III. A growing body of evidence suggests that underlying disturbance in circadian rhythm functioning may explain sleep problems within the MPS III population. METHODS: Actigraphic data were recorded in eight children with MPS III over 7-10 days and compared to age-matched typically developing controls. Parameters of circadian rhythmicity and activity levels across a 24-h period were analysed. RESULTS: Statistically and clinically significant differences between the two groups were noted. Analysis indicated that children with MPS III showed significantly increased fragmentation of circadian rhythm and reduced stability with external cues (zeitgebers), compared to controls. Average times of activity onset and offset were indicative of a phase delayed sleep-wake cycle for some children in the MPS III group. Children with MPS III had significantly higher activity levels during the early morning hours (midnight-6 am) compared to controls. CONCLUSIONS: Results are consistent with previous research into MPS III and suggest that there is an impairment in circadian rhythm functioning in children with this condition. Implications for clinical practice and the management of sleep difficulties are discussed.

Assessment of sleep in children with mucopolysaccharidosis type III.

Sleep disturbances are prevalent in mucopolysaccharidosis Type III (MPS III), yet there is a lack of objective, ecologically valid evidence detailing sleep quantity, quality or circadian system. Eight children with MPS III and eight age-matched typically developing children wore an actigraph for 7-10 days/nights. Saliva samples were collected at three time-points on two separate days, to permit analysis of endogenous melatonin levels. Parents completed a sleep questionnaire and a daily sleep diary. Actigraphic data revealed that children with MPS III had significantly longer sleep onset latencies and greater daytime sleep compared to controls, but night-time sleep duration did not differ between groups. In the MPS III group, sleep efficiency declined, and sleep onset latency increased, with age. Questionnaire responses showed that MPS III patients had significantly more sleep difficulties in all domains compared to controls. Melatonin concentrations showed an alteration in the circadian system in MPS III, which suggests that treatment for sleep problems should attempt to synchronise the sleep-wake cycle to a more regular pattern. Actigraphy was tolerated by children and this monitoring device can be recommended as a measure of treatment success in research and clinical practice.

An investigation of the middle and late behavioural phenotypes of Mucopolysaccharidosis Type-III.

BACKGROUND: Mucopolysaccharidosis type-III (MPS III) is an autosomal recessive lysosomal storage disorder. It causes progressive physical and cognitive decline and has been linked to increased incidences of behavioural problems. METHODS: Data on the behaviour and adaptive skills of 20 children with MPS III and 25 children with intellectual disability (ID) (17 included in analysis) were gathered via parental report questionnaire. The frequencies of different types of behaviour displayed by children with MPS III and children with ID were compared across two age categories. RESULTS: The total frequency of challenging behaviours displayed by children aged 2-9 years with MPS III and ID was not significantly different. Behaviours associated with hyperactivity, orality, unusual body movements and inattention were seen significantly more frequently in 2-9 year olds with MPS III than in those with ID. Children aged 10-15 years with MPS III showed significantly fewer problem behaviours than a contrasting group with ID. The frequency of challenging behaviours displayed by children with MPS III and their adaptive skills was found to decrease with age. CONCLUSIONS: Behaviours relating to hyperactivity, orality, unusual body movements and inattention are part of the behavioural phenotype of the middle phase of MPS III. The late phase of MPS III is associated with low rates of problem behaviour and loss of adaptive skills. Therefore, families with a child with MPS III may benefit from a different type of clinical service when the child is aged 2-9 years, than when aged 10-15 years.

Object specificity and personal relevance in long-term visual remembering.

The personal relevance of an object is multi-faceted, each facet being capable of contributing to the effects on object memory attributed to personal relevance. An object's status as an individual object (object specificity), rather than just a category of object, is one such facet and its impact on the long-term visual remembering of everyday objects is assessed in two experiments. Images and drawings were produced under generic (e.g., "Please draw a bed") and personal exemplar (e.g., "Please draw your bed") instructions, and participants indicated the degree to which the image on which their drawing was based was of a specific object or a generic object. Object specificity induced a sense of time and place for a remembered object, the most recent encounter with the object being most salient. Other aspects of personal relevance collectively facilitated the retrieval of an object's category-irrelevant features (thereby increasing the vividness of the object image), the other objects with which it was seen, and a more general episodic sense of place. Against a broader theoretical perspective, it is proposed that visual episodic memory and visual knowledge are primary sources of information for specific personally relevant objects and generic objects, respectively.

Parental social support, coping strategies, resilience factors, stress, anxiety and depression levels in parents of children with MPS III (Sanfilippo syndrome) or children with intellectual disabilities (ID).

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of four enzymes involved in the catabolism of the glycosaminoglycan heparan sulphate. It is a degenerative disorder, with a progressive decline in children's intellectual and physical functioning. There is currently no cure for the disorder. To date there is a paucity of research on how this disorder impacts parents psychological functioning. Specifically, research in the area has failed to employ adequate control groups to assess if the impact of this disorder on parents psychological functioning differs from parenting a child with intellectual disability (ID). The current study examined child behaviour and parental psychological functioning in 23 parents of children with MPS III and 23 parents of children with ID. Parents completed postal questionnaires about their child's behaviour and abilities and their own psychological functioning. Parents of children with MPS III reported fewer behavioural difficulties as their child aged, more severe level of intellectual disability, and similar levels of perceived social support, coping techniques, stress, anxiety and depression levels as parents of children with ID. Both groups of parents scored above the clinical cut off for anxiety and depression. Parents of children with MPS III rated themselves as significantly less future-orientated and goal directed than parents of children with ID. Services should develop support packages for parents of children with MPS III that incorporate an understanding of the unique stressors and current-difficulty approach of this population. Future research should examine gender differences between parental psychological functioning, using mixed qualitative and quantitative approaches, and utilise matched developmental level and typically developing control groups.