Assessment of Sleep in Children with Mucopolysaccharidosis Type III

Abstract

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.

Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III

“…early language, loss of walking, cognitive delay, abnormal behaviours, school levelEnzyme activity in leukocytes or fibroblastsDNA sequencingGrant et al(2013)[81]UKParents (23) of children with MPS III (19)Parents (23) of children with ID (20)Child behaviour and parental psychological functioning. Questionnaire packs sent out to families and completed at a single time point.Behaviour: LDCMS, ECBIParental psychological functioning: Resilience Scale for Adults, Multidimensional Scale of Perceived Social Support, coping techniques (Brief COPE questionnaire), Paediatric Inventory for Parents, parental anxiety and depression (General Health Questionnaire, GHQ-12)Delgadillo et al (2013)[24]SpainMPS IIIA (34)MPS IIIB (11)MPS IIIC (10)Retrospectively collected data using a questionnaire answered by physicians and parentsQuestionnaire: early psychomotor development, age at diagnosis, first clinical symptoms, somatic features, speech, behavioural and sleep disturbance, evolution of neurodegenerative symptoms, age at regression of acquired skills and loss of functional abilities, feeding, cognitive failure through the disease, orthopaedic complications, deathDetails of previously conducted enzyme assays and mutation analysisMahon et al(2014) [76]UKMPS IIIA (4)MPS IIIB (4)Prospective study over 7 days of eight children with MPS III and eight age-matched typically developing controlsActigraphySalivary melatonin concentrationsSleep questionnaire and daily sleep diaryCross et al2014[108]UKMPS III (20)ID (24)Assessment of behaviour and adaptive skills. Questionnaire packs sent out to families and completed at a single time point.Behaviour: LDCMS, ECBI, Aberrant Behaviour Checklist, SBRSAdaptive skills: VABS-IIBuhrman et al (2014)[60]USAMPS IIIA (46)Retrospectively collected data using a standardised protocol of assessments conducted at a single visit by an MDT (neurodevelopmental pediatricians, speech and language pathologists, developmental specialists, psychologists, audiologists, physical therapists)Age at diagnosis and initial symptoms,Audiology assessmentsCognitive function, adaptive behaviour, expressive and receptive language, motor development (neuropsychological instruments not specified)Behavioural symptomsSomatic symptomsGrowth parameters (height, weight, BMI, head circumference)SurvivalMumford et al(2015)[77]UKMPS IIIA (4)MPS IIIB (4)Prospective study of children with MPS III and age-matched typically developing controls over 7–10 daysActigraphyShapiro et al(2016)[58]USAMPS IIIA (25)Longitudinal data collected prospectively over a 2 year follow up period with evaluations at baseline, 6 months, 12 months and 2 yearsCognitive assessments (KABC-II or BSID-III), reported as age equivalent scores and DQsAdaptive behaviour (VABS-II), age equivalent...…”

Epilepsy in Children With Mucopolysaccharidosis: Epidemiology, Clinical and Electroencephalographic Features

“…Известно также, что частота эпилепти-ческих приступов увеличивается с прогрессированием нейрокогнитивных нарушений [6,25]. Кроме того, выяв-лена аггравация приступов при нарушениях сна и умень-шении продолжительности ночного сна [26].…”

Otolaryngological findings in mucopolysaccharidosis

“…[25][26][27] Incidence varies across countries with 1.21 per 100,000 babies affected in the UK. [25][26][27] MPS III has three phases, [28] with the first phase (1-4 years) characterized by developmental delay, the second phase (4-10 years) by behavioral disturbance, including sleep difficulties, aggressive or destructive behaviors, hyperactivity and attention difficulties, and the third/end phase (10+ years) by progressive loss of skills (especially language), seizures, and problems with mobility and swallowing. The four subtypes of MPS III A-D correspond to variations in enzyme deficiency, with A and B being the most common and D the rarest.…”

“…There is little clinical difference between subtypes, [28] but A might show a more severe course [29] and C a more attenuated course. [27,30] Sanfilippo syndrome results from the deficiency or absence of 4 different enzymes that are necessary to degrade the GAG heparan sulfate. Each enzyme deficiency defines a different subtype of Sanfilippo syndrome, as follows: type IIIA (Sanfilippo A), type IIIB (Sanfilippo B), type IIIC (Sanfilippo C), and type IIID (Sanfilippo D).…”

“…However, classic clinical features are an abundance of coarse facial and body hair (hirsutism). [37] Otolaryngological manifestations in MPS III (Table 3) • Dense calvaria • Joint stiffness • Mild coarse facial features • Synophrys: presence of abundant hair between the eyebrows • Hearing loss with speech delay • Sleep disturbances [27] …”