Combined Behavioral, Pharmacological Therapy Seems to be Best in Treating MPS Disorders

Combined behavioral and pharmacological therapy seems to be the best course of action in treating behavioral and sleep problems in children with mucopolysaccharidosis (MPS) disorders, a review study has found.

MPS comprises a group of lysosomal storage disorders caused by deficiencies and/or malfunction of specific enzymes responsible for breaking down large complex sugar molecules, called glycosaminoglycans (GAGs), leading to the formation and accumulation of toxic deposits in cells and tissues from different parts of the body.

The review study, “Practical management of behavioral problems in mucopolysaccharidoses disorders,” published in Molecular Genetics and Metabolism, summarized the most recent findings regarding behavioral and sleeping problems in MPS disorders, as well as the best treatment strategies to manage them.

Discussed findings were based on data presented by a group of 39 experts in managing and treating MPS disorders during the international meeting “The Brain in MPS: Today and Tomorrow,” held in 2016 in Stockholm, Sweden.

Behavioral problems (hyperactivity, temper tantrums, lack of fear, disobedience/unresponsiveness to discipline, and destructive behavior) and sleep disturbances are among the most common neurological symptoms observed in children with MPS I, II, III, and VII.

These behavioral abnormalities seem to be more prevalent in MPS III (also known as Sanfilippo syndrome) and MPS II, and tend to manifest early in life (ages 2-4). Probably due to progressive cognitive and motor decline, these behavioral problems eventually diminish after ages 8-9.

Besides behavioral problems, these children often experience sleep disturbances (settling difficulties, waking up during the night, insomnia, wandering around the house, screaming, singing and/or laughing at night, early morning awakening, and daytime sleeping), which seem to be correlated with behavioral issues they experience while awake.

“Although it remains uncertain how sleep problems affect daytime behavior and vice versa in MPS patients, an interaction seems likely. Studies in other diseases have shown associations between sleep disorders/daytime sleepiness and dementia/cognitive decline,” researchers said.

Although behavioral and sleep problems in children with MPS I, II, and III can be a direct consequence of neurodegeneration caused by GAG accumulation in neurons, there are other factors that can contribute to worsening these issues, including muscle or abdominal pain, high intracranial pressure and seizures.

“The physical factors discussed above may coexist in MPS patients, and it is important to consider each of them early on as they can often be successfully treated,” researchers said. “If physical factors are excluded, behavioral abnormalities can be managed through practical interventions, environmental changes, behavioral therapy, and/or medication.”

Different types of interventions have been proposed to minimize behavioral and sleep issues among children with MPS disorders. Practical interventions carried out by parents or caregivers to create a safe home environment, with established routines and schedules, could be the first step in addressing these issues.

Other studies noted that behavioral therapies and different types of medication (anti-psychotics, stimulants, mood stabilizers, antihistamines, melatonin, and anti-anxiety drugs) seem to be more effective when used together rather than alone.

In the parental survey study — where parents of MPS III patients were surveyed to investigate their children’s experiences of sleep disturbance and evaluate treatments’ success in dealing with these issues — 50% of the parents using behavioral therapy in combination with medication “believed this combination to be more effective in treating sleep disturbances than a single approach,” researchers said.

Finally, the authors believe it is crucial that carers and family members take time off and rest, both physically and emotionally, to be able to cope with day-to-day challenges and stress associated with MPS child care.

“Managing behavioral problems in children with MPS II and III can be very challenging for the family.  Therefore, it is important that health care professionals, closely involved in the care and
support for MPS patients, regularly evaluate how parents and family are coping with stressful situations and provide advice or referral to a specialized center or support group when needed,” they concluded.