Sustained improvement of refractory sleep disturbance and agitation with low-dose quetiapine in Sanfilippo Syndrome

INTRODUCTION

Mucopolysaccharidosis type III (Sanfilippo syndrome) is a progressive lysosomal storage disorder, predominantly affecting the central nervous system, characterized by neurodevelopmental regression following an initial period of normal development in early childhood. Behavioral disturbances and severe sleep abnormalities are among the most prominent clinical features and are reported in the majority of patients[1]. Sleep disturbances in this population are typically characterized by prolonged sleep latency, frequent nocturnal awakenings, and disruption of circadian rhythm[1]. The underlying mechanisms are multifactorial, involving circadian dysregulation, altered melatonin secretion, and progressive neurodegeneration[2,4]. In this report, we describe a patient with treatment-resistant sleep disturbance and agitation who demonstrated a sustained clinical response to low-dose quetiapine.

CASE PRESENTATION

A 13-year-old female patient with a diagnosis of Sanfilippo syndrome was referred to our clinic due to severe sleep disturbance and associated agitation. Her early developmental milestones were reported as normal until the age of 3 years, after which she exhibited progressive neurodevelopmental regression. She lost her speech approximately 5 years prior to presentation and had been non-ambulatory for the past 3 years.

According to the caregiver, sleep disturbances had been present for approximately 4–5 years. The patient experienced prolonged sleep latency of up to 2–3 hours and frequent nocturnal awakenings, occurring up to 4–5 times per night. These disturbances were associated with significant behavioral dysregulation, including evening crying spells, irritability, and episodes of agitation with self-injurious behavior, particularly when sleep-deprived.

Previous pharmacological interventions included hydroxyzine, which provided partial benefit for approximately 3 months before losing efficacy.Treatment with risperidone resulted in marked sedation without improvement in sleep disturbances.

Sleep hygiene measures were introduced, and melatonin was initiated at 1 mg/day.Although transient improvement was observed during the first 3 days, sleep disturbances recurred. Increasing the dose to 3 mg/day did not yield additional benefit and was associated with increased restlessness and prominent pre-sleep leg movements, leading to discontinuation.

Due to persistent symptoms, quetiapine was initiated at a dose of 12.5 mg/day. Following initiation of treatment, a marked improvement in sleep parameters was observed. Sleep latency decreased from 2–3 hours to minimal levels, with the patient able to fall asleep easily in the early evening. Total sleep duration increased to approximately 8 hours per night, and nocturnal awakenings decreased from 4–5 times to once per night or less, with some nights remaining uninterrupted.

The patient has been maintained on quetiapine 12.5 mg/day for one year, with sustained clinical benefit and no reported adverse effects.

CONCLUSION

This case suggests that low-dose quetiapine may be an effective and well-tolerated option for managing refractory sleep disturbance and associated agitation in patients with Sanfilippo syndrome. In this case, treatment with melatonin was ineffective, which is consistent with previous reports indicating variable efficacy and inconsistent treatment responses in this patient population[3]. In our patient, quetiapine treatment resulted in marked improvement in sleep and behavioral symptoms, with sustained benefit over a one-year follow-up period. These findings suggest that quetiapine may represent a valuable therapeutic alternative, particularly in cases that are refractory to other treatments; however, further studies are needed to confirm its efficacy and safety in this population.

References

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3. Mumford RA, Mahon LV, Jones S, Bigger B, Canal M, Hare DJ. Actigraphic investigation of circadian rhythm functioning and activity levels in children with mucopolysaccharidosis type III (Sanfilippo syndrome). J Neurodev Disord. 2015;7(1):31. doi: 10.1186/s11689-015-9126-5. Epub 2015 Sep 1. PMID: 26388955; PMCID: PMC4574189.
4. .Rigante D, Veredice C. Neuroinflammation as a Novel Therapeutic Frontier for Sanfilippo Syndrome. Children (Basel). 2025 Nov 12;12(11):1530. doi: 10.3390/children12111530. PMID: 41300647; PMCID: PMC12651789.