Abstract
Children with mucopolysaccharidosis IIIA (MPS-IIIA) may receive a diagnosis of autism spectrum disorder (ASD) due to MPS-IIIA’s initial symptom similarities with ASD. This may lead to professionals receiving referrals to work with these children but unaware of how these children may respond differently to treatment. To appropriately work with these children, clinicians must obtain knowledge of the symptoms, progressions, regression, comorbidities, and clinical interventions. This manuscript guides clinicians on the discrimination of MPS-IIIA from ASD for (a) physiological symptoms, (b) skill development and regression of skills, and (c) behavior problems from infancy to adolescence. The manuscript also provides available intervention research.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
As prevalence of autism spectrum disorders (ASD) has increased to 1 in 59 children (Baio et al., 2018), clinicians concentrate on investigating relations among ASD phenotypes and disorders which share similarities with ASD (Cohen et al., 2005; Moss & Howlin, 2009; Rumsey et al., 2014). Clinicians may be less familiar with disorders that share symptomology and similarities (e.g., social communication deficits; restricted, repetitive behavior; problem behavior; and sleep problems: American Psychiatric Association, 2013) yet have different developmental and treatment trajectories. For example, mucopolysaccharidosis-IIIA (MPS-IIIA; Sanfilippo syndrome), a lysosomal storage disease, results in central nervous system (CNS) damage. This damage results in progressive physiological symptoms and regression of skills as children age, despite early skill and behavior development resembling ASD and responses to intervention (Rumsey et al., 2014; Wijburg, et al., 2013; Wolfenden, et al., 2017).The rarity of MPS-IIIA (1 in 100,000 children) explains clinicians’ lack of exposure to the disease and symptoms’ similarities to ASD (Fedele, 2015; Heron et al., 2010; Rumsey et al., 2014; Sorrentino & Fraldi, 2016; Wijburg et al., 2013; Wolfenden et al., 2017).
Clinicians who specialize in ASD may receive referrals to work with these children before an MPS-IIIA diagnosis. Non-medical clinicians may be the first professional families access. Although clinicians may suspect a difference, lack of exposure to MPS-IIIA may hinder identification. Failure in early identification of MPS-IIIA restricts medical research and treatment support for children with a limited lifespan. Since no cure or physiological treatments exist for the CNS degeneration in MPS-IIIA (Cleary & Wraith, 1993; Fedele, 2015; Sorrentino & Fraldi, 2016; Stapleton et al., 2019; Valstar et al., 2008), clinicians must learn the progression of MPS-IIIA to provide interdisciplinary and appropriate interventions to improve the quality of life for these children and families beyond just palliative care (Cleary & Wraith, 1993; Ghosh et al., 2017; Grant, 2021; Shapiro et al., 2016; Stapleton et al., 2019; Wijburg et al., 2013). This paper provides a guide to identifying MPS-IIIA and suggestions for applications of non-medical, existing interventions.
Symptoms and Progression: Discriminating MPS-IIIA from ASD
Physiological
From infancy, children with MPS-IIIA exhibit facial characteristics and medical conditions subtly differentiating them from other children with ASD (see Table 1). Physiological symptoms gradually worsen during young childhood. During pre-adolescence, children with MPS-IIIA experience significant physical regression and worsening comorbid medical conditions (Shapiro et al., 2018; Valstar et al., 2008; Wijburg et al., 2013; Wolfenden et al., 2017). Physical health and mobility diminish leading to early death (average 15 years old: range 8.5–29 years) often from physiological complications (Cleary & Wraith, 1993; Delgadillo et al., 2013; Heron et al., 2010; Malm & Mansson, 2010; Meyer et al., 2007; Valstar et al., 2008, 2010; van de Kamp et al., 1981; Wijburg et al., 2013).
Cognitive, Communication, and Social
In infancy, MPS-IIIA may be difficult for clinicians to detect (Bax & Colville, 1995; Ghosh et al., 2017; Meyer et al., 2007; Valstar et al., 2010) with one-fourth of infants developing typical social, communication, and cognitive skills (Meyer et al., 2007; Nidiffer & Kelly, 1983). As a toddler (e.g., 1–4 years old), they exhibit more distinct differences, resembling the social, communication, and cognitive development of children with ASD, such as missed developmental milestones, delayed speech, echolalia, lack of eye contact, and fewer social interactions (Buhrman et al., 2014; Cleary & Wraith, 1993; Cohen et al., 2005; Heron et al., 2010; Malm & Mansson, 2010; Nidiffer & Kelly, 1983; Rumsey et al., 2014; Shapiro et al., 2015; van de Kamp et al., 1981; Wijburg et al., 2013; Wolfenden et al., 2017). See Table 1 for symptoms and progressions.
For those with speech, communication regression occurs as early as 2 to 4 years old (Bax & Colville, 1995; Buhrman et al., 2014; Meyer et al., 2007; Wijburg et al., 2013), which may resemble regressive ASD versus early onset autism (Ozonoff, et al., 2005). As in ASD, communication difficulties co-occur with social skill problems, such as delayed communication co-occurring with lack of gesture use, play skills, and joint attention (Cohen et al., 2005; Nidiffer & Kelly, 1983; Rumsey et al., 2014; Wolfenden et al., 2017). By 3 to 4 years old, social communication skills so highly resemble ASD that toddlers with MPS-IIIA often receive an ASD diagnosis often without the accompanying MPS-IIIA diagnosis (Rumsey et al., 2014; Wijburg et al., 2013; Wolfenden et al., 2017).
Impaired cognitive ability and increased communication deficits resembling ASD become more obvious as the child ages (Buhrman et al., 2014; Cleary & Wraith, 1993; Cohen et al., 2005; Delgadillo et al., 2013; Heron et al., 2010; Malm & Mansson, 2010; Meyer et al., 2007; Nidiffer & Kelly, 1983; Rumsey et al., 2014; Schreck et al., 2018; Shapiro et al., 2016; Valstar et al., 2010; van de Kamp et al., 1981; Wijburg et al., 2013; Wolfenden et al., 2017). Children continue to experience delays and exhibit symptoms similar to ASD (e.g., delayed speech, loss of eye contact, restricted facial expressions) until experiencing a regression. Young children with MPS-IIIA (e.g., 4–10 years old) with rapid progression experience severe regression resembling dementia such as memory loss, diagnoses of intellectual disabilities, loss of understanding and use of words, and reduced interactions with others (Buhrman et al., 2014; Delgadillo et al., 2013; Malm & Mansson, 2010; Meyer et al., 2007; Nidiffer & Kelly, 1983; Schreck et al., 2018; Shapiro et al., 2016; Shapiro & Eisengart, 2021; Sorrentino & Fraldi, 2016; Truxal et al., 2016; Valstar et al., 2008; van de Kamp et al., 1981; Wijburg et al., 2013). Those experiencing slower regression eventually experience a similar end result loss of skills (Shapiro et al., 2016). Once speech regression begins, loss of words occurs quickly with total loss of speech and cognitive abilities typically occurring by 8 years old (Buhrman et al., 2014; Delgadillo et al., 2013; Schreck et al., 2018). Regression of receptive language occurs more gradually than loss of expressive speech (Buhrman et al., 2014). This regression and loss of skills also occur for social skills (Buhrman et al., 2014; Delgadillo et al., 2013; Nidiffer & Kelly, 1983; Schreck et al., 2018; Shapiro et al., 2016; Sorrentino & Fraldi, 2016; Valstar et al., 2011).
The skill regression for children with MPS-IIIA can result in diagnostic differentiation by 4 years old for clinicians aware of MPS-IIIA (Colville & Bax, 1996; Meyer et al., 2007). Even for clinicians less familiar with MPS-IIIA, the continued regression of skills differentiates pre-adolescents with MPS-IIIA. By pre-adolescence, ability to communicate typically disappears (Meyer et al., 2007; Nidiffer & Kelly, 1983; Shapiro et al., 2018; Valstar, et al., 2018). Additionally, adolescents lose the social skills that began to deteriorate during young childhood. By 10 years old, pre-adolescents to adolescents (e.g., 10 + years old) may completely lose the ability to socially relate to others (Heron et al., 2010).
Motor and Related Skills
Infants and toddlers have gross and fine motor skills sometimes occurring within normal developmental time periods and developing into social and adaptive use of motor skills (Bax & Colville, 1995; Buhrman et al., 2014; Cleary & Wraith, 1993; Delgadillo et al., 2013; Heron et al., 2010; Malm & Mansson, 2010; Nidiffer & Kelly, 1983; Schreck et al., 2018; Shapiro et al., 2015; van De Kamp et al., 1981. In young childhood, motor difficulties resemble those of children with ASD (Table 1 provides symptoms and progressions). However, unlike children with just an ASD diagnosis, children with MPS-IIIA experience significant motor and adaptive behavior regression from 4 to 10 years old (Buhrman et al., 2014; Shapiro et al., 2016), losing toileting and feeding skills (Cleary & Wraith, 1993; Niddifer & Kelly, 1983), and experiencing movement or balance problems and regression of walking (Buhrman et al., 2014; Cleary & Wraith, 1993; Delgadillo et al., 2013; Mariotti et al., 2003; Schreck et al., 2018; Shapiro et al., 2018). By adolescence, physiological symptoms worsen effecting motor skills (Cleary & Wraith, 1993; Meyer et al., 2007; Valstar et al., 2008; Wijburg et al., 2013). Most motor skills regress or disappear by approximately 12 years—adolescence (Meyer et al., 2007) with increased falls and total loss of walking, difficulty or inability to swallow, and complete immobility and unresponsiveness until death (Buhrman et al., 2014; Cleary & Wraith, 1993; Fedele, 2015; Heron et al., 2010; Malm & Mansson, 2010; Mariotti et al., 2003; Schreck et al., 2018; Shapiro et al., 2018; Valstar et al., 2008; Wijburg et al., 2013).
Behavior Problems
Toddlers and young children with MPS-IIIA exhibit behavior problems similar to those with ASD, such as sleep problems, problem behaviors, restricted interests/stereotypy, attention deficit hyperactivity disorder, and anxiety (Bax & Colville, 1995; Buhrman et al., 2014; Cleary & Wraith, 1993; Cohen et al., 2005; Colville, et al., 1996; Cross & Hare, 2013; Delgadillo et al., 2013; Fraser, et al., 2005; Fraser, et al., 2002; Heron et al., 2010; Hoffman et al., 2020; Mahon et al., 2014; Mariotti et al., 2003; Meyer et al., 2007; Nidiffer & Kelly, 1983; Rumsey et al., 2014; Schreck et al., 2018; Shapiro et al., 2015; Valstar et al., 2008; van de Kamp et al., 1981; Wijburg et al., 2013; Wolfenden et al., 2017). These diverse behaviors begin and worsen from 3 to 5 years old and increase into young childhood (Bax & Colville, 1995; Buhrman et al., 2014; Cleary & Wraith, 1993; Colville et al., 1996; Fraser et al., 2005; Ghosh et al., 2017; Heron et al., 2010; Malcolm, et al., 2012; Mariotti et al., 2003; Meyer et al., 2007; Nidiffer & Kelly, 1983; Rumsey et al., 2014; Schreck et al., 2018; Shapiro et al., 2015, 2018; Truxal et al., 2016; Valstar et al., 2010; Wijburg et al., 2013). In young childhood, they also may develop other behaviors resulting in an ASD diagnosis, such as self-injurious behavior, lethargy, disrobing, perseverative mouthing behavior, mood swings and crying, and separation anxiety (Bax & Colville, 1995; Buhrman et al., 2014; Cohen et al., 2005; Malcolm et al., 2012; Nidiffer & Kelly, 1983; Rumsey et al., 2014; Schreck et al., 2018; Shapiro et al., 2015; Valstar et al, 2010; Wolfenden et al., 2017; Wijburg et al., 2013.
By pre-adolescence/adolescence, behavioral symptoms differentiate them from their peers. Although sleep disturbances can remain problematic, other behaviors tend to decrease or disappear (Buhrman et al., 2014; Cleary & Wraith, 1993; Colville et al., 1996; Ghosh et al., 2017; Mariotti et al., 2003; Nidiffer & Kelly, 1983; Schreck et al., 2018; Valstar et al., 2008, 2010; Wijburg et al., 2013), possibly due to physiological progression of the disease impeding behavior problems (Buhrman et al., 2014; Cleary & Wraith, 1993; Wijburg et al., 2013). However, crying/mood swings may maintain, even in absence of any obvious signs of pain (Cleary & Wraith, 1993; Shapiro et al., 2018).
Interventions
Physiological
Physiological interventions for all ages of children with MPS-IIIA remain symptom and location-based, for example, seizure medication, ear tube implants, hearing aids, glasses, and physical therapy or splints for scoliosis, pain, and contractures (Buhrman et al., 2014; Cleary & Wraith, 1993; Meyer et al., 2007; Wijburg et al., 2013. No intervention exists for the physiological CNS regression or cause of MPS-IIIA (Buhrman et al., 2014; Fedele, 2015). CNS degeneration contributes to clinician’s differentiation of MPS-IIIA allowing for additional pharmacologic and nutritional symptom interventions to improve comfort and quality of life. However, the empirically supported evidence for the effectiveness of these interventions remains equivocal (Cleary & Wraith, 1993).
Social, Communication, Cognitive, Motor, and Adaptive
Although research supported behavioral interventions exist for instruction of social, communication, cognitive, motor, and adaptive skills for children with ASD (National Autism Center, 2009, 2015), only one report of teaching skills for a pre-adolescent with MPS-IIIA was located (Schreck et al., 2018). Schreck and colleagues (2018) used behavioral interventions to teach (a) use of an augmentative communication device for requesting (e.g., foods, people, activities) in multiple environments after verbal regression, (b) acquisition and maintenance of motor skills, (c) use of play skills, and (d) maintenance of adaptive behavior. Additionally, some researchers suggest that interventions and physical therapy commonly used in ASD instruction may result in partial success for teaching and maintaining mobility, toileting, hygiene, and feeding (Cleary & Wraith, 1993; Nidiffer & Kelly, 1983; Schreck et al., 2018). These recommendations suggest that children with MPS-IIIA can learn and maintain skills to improve quality of life; however, controlled research must be conducted to determine instructional methods. Until then, clinicians must generalize from effective interventions for children with ASD (National Autism Center, 2009, 2015; Rumsey et al., 2014).
Behavior Problems
Very few research studies provide clinical recommendations for reducing behavior problems specifically in this population. Recommendations remain mostly hypothetical or contradicting. For example, some research supports using pharmacological treatments, such as antipsychotics, melatonin, benzodiazepines, and seizure medications (Cleary & Wraith, 1993; Fraser et al., 2002, 2005; Guerrero, et al., 2006; Hoffman et al., 2020; Nidiffer & Kelly, 1983; Valstar et al., 2008) and contends the lack of effectiveness of behavioral interventions (Cleary & Wraith, 1993; Wijburg et al., 2013). Others suggest pharmacological treatments may be mostly entirely ineffective or requires significant precautions (Cleary & Wraith, 1993; Hoffman et al., 2020; Nidiffer & Kelly, 1983; Valstar et al., 2008; Wijburg et al, 2013), and behavioral treatments show promise (Colville et al., 1996; Escolar, et al., 2017; Fraser et al., 2002, 2005; Nidiffer & Kelly, 1983; Schreck et al., 2018; Valstar et al., 2008; Wijburg et al., 2013). No studies directly and empirically evaluate the effectiveness of pharmacological treatment or its interaction with behavioral interventions as recommended for Intellectual and Developmental Disability populations (IDD: Napolitano et al., 1999; Sprague & Werry, 1971). Two studies indicate the possible effectiveness of behavioral interventions (sleep problems, Colville et al. (1996); pica, hand mouthing, tantrums, Schreck et al. (2018)). Thus, clinicians’ intervention choices remain significantly limited to preliminary evidence. Until more research exists, professionals must choose interventions from effective interventions for children with ASD/IDD (National Autism Center, 2015; Rumsey et al., 2014) which include function-based treatments (e.g., attention, tangibles, automatic, escape/avoidance) that may be related to behavioral topography (Matson et al., 2011; Williams & McAdam, 2012).
Conclusion
Children with MPS-IIIA exhibit skill deficits and behavior problems initially resembling the symptomatic patterns of children with ASD, often leading to a diagnosis of ASD (Rumsey et al., 2014; Wolfenden et al., 2017). Due to their ASD diagnoses and the effectiveness of behavior interventions in ASD (National Autism Center, 2009, 2015), clinicians may receive referrals to provide behavioral interventions to alter environmental stimuli (e.g., changing antecedent conditions and assessing and treating behaviors according to functions). Although preliminary research suggests that these behavioral interventions may be effective (Colville et al., 1996; Schreck et al., 2018), children with MPS-IIIA’s response may differ from their peers with ASD who do not have the underlying physiological degeneration. For example, interventions may initially result in communication acquisition, but not maintenance. Further, a comprehensive and interdisciplinary (medical and behavioral) approach may be necessary to treat physiological symptoms (e.g., pain, seizures, and contractures) in conjunction with behavior (see Milnes and Piazza (2013) for example of this approach in another population). Without exposure to MPS-IIIA, clinicians may choose inappropriate learning objective goals (e.g., continuing verbal instruction in place of augmentative communication) or may struggle with providing appropriate treatment.
As no cure for MPS-IIIA exists and clinical intervention primarily concentrates on reducing physiological symptoms (Fedele, 2015; Sorrentino & Fraldi, 2016) or palliative care (Cleary & Wraith, 1993; Stapleton et al., 2019; Wijburg et al., 2013), clinicians must expand the research based on skill acquisition, skill maintenance, and behavior problem reduction. Additionally, clinicians should investigate the effects of early intervention on the effectiveness of treatments (Shapiro et al., 2016) which may allow clinicians to teach alternative or modified skills before skill and behavioral regression. Addressing skills and behavioral issues have been identified as pre-eminent in increased quality of life, continued interactions, and familial adjustment (Buhrman et al, 2014; Portera et al., 2020; Ghosh et al., 2017; Grant, 2021). Developing effective, individualized interventions for children with MPS-IIIA may lead to more positive and effective interactions with their families and peers and increased maintenance of independence. Until a cure can be found, clinicians must strive to maintain or increase the quality of these children’s and their families’ lives.
References
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596
Baio, J., Wiggins, L., Christensen, D., Maenner, M., Daniels, J., Warren, Z., & Dowling, N. (2018). Prevalence of autism spectrum disorder among children aged 8 years – Autism and developmental disabilities monitoring network, 11 sites, United States, 2014. Morbidity and Mortality Weekly Report, 67(6), 1–23. https://doi.org/10.15585/mmwr.ss6706a1
Bax, M. C., & Colville, G. A. (1995). Behaviour in mucopolysaccharide disorders. Archives of Disease in Childhood, 73(1), 77–81.
Buhrman, D., Thakkar, K., Poe, M., & Escolar, M. L. (2014). Natural history of Sanfilippo syndrome type A. Journal of Inheritable Metabolic Disorders, 37, 431–437. https://doi.org/10.1007/s10545-013-9661-8
Cleary, M. A., & Wraith, J. E. (1993). Management of mucopolysaccharidosis type III. Archives of Disease in Childhood, 69(3), 403–406.
Cohen, D., Pichard, N., Tordjman, S., Baumann, C., Burglen, L., Excoffier, E., & Heron, D. (2005). Specific genetic disorders and autism: Clinical contribution towards their identification. Journal of Autism and Developmental Disorders, 35(1), 103–116. https://doi.org/10.1007/s10803-004-1038-2
Colville, G. A., & Bax, M. A. (1996). Early presentation in the mucopolysaccharide disorders. Child: Care Health and Development, 22(1), 31–36. https://doi.org/10.1111/j.1365-2214.1996.tb00420.x
Colville, G. A., Watters, J. P., Yale, W., & Bax, M. (1996). Sleep problems in children with Sanfilippo syndrome. Developmental Medicine and Child Neurology, 38(6), 538–544. https://doi.org/10.1111/j.1469-8749.1996.tb12114.x
Cross, E. M., & Hare, D. J. (2013). Behavioural phenotypes of the mucopolysaccharide disorders: A systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders. Journal of Inherited Metabolic Disorders, 36, 189–200. https://doi.org/10.1007/s10545-012-9572-0
Delgadillo, V., O’Callaghan, M. D., Gort, L., Coll, M., & Pineda, M. M. (2013). Natural history of Sanfilippo syndrome in Spain. Orphanet Journal of Rare Diseases, 8, 189. https://doi.org/10.1186/1750-1172-8-189
Escolar, M. L., Jones, S. A., Shapiro, E. G., Horovitz, D. D., Lampe, C., & Amartino, H. (2017). Practical management of behavioral problems in mucopolysaccharidoses disorders. Molecular Genetics and Metabolism, 122(Suppl), 35–40. https://doi.org/10.1016/j.ymgme.2017.09.010
Fedele, A. O. (2015). Sanfilippo syndrome: Causes consequences and treatments. The Application of Clinical Genetics, 8, 269–281. https://doi.org/10.2147/TACG.S57672
Fraser, J., Gason, A. A., Wraith, J. E., & Delatycki, M. B. (2005). Sleep disturbance in Sanfilippo syndrome: A parental questionnaire study. Archives of Disease in Childhood, 90(12), 1239–1242. https://doi.org/10.1136/adc.2004.065482
Fraser, J., Wraith, J. E., & Delatycki, M. B. (2002). Sleep disturbance in mucopolysaccharidosis type III (Sanfilippo syndrome): A survey of managing clinicians. Clinical Genetics, 62, 418–421. https://doi.org/10.1034/j.1399-0004.2002.620512.x
Guerrero, J. M., Pozo, D., Diaz-Rodriguez, J. L., Martinez-Cruz, F., & Vela-Campos, F. (2006). Impairment of the melatonin rhythm in children with Sanfilippo syndrome. Journal of Pineal Research, 40(2), 192–193. https://doi.org/10.1111/j.1600-079X.2005.00294.x
Ghosh, A., Shapiro, E., Rust, S., Delaney, K., Parker, S., Shaywitz, A., Morte, A., Bubb, G., Cleary, M., Bo, T., Lavery, C., Bigger, B. W., & Jones, S. A. (2017). Recommendations on clinical trial design for treatment of mucopolysaccharidosis type III. Orphanet Journal of Rare Diseases, 12, 1–15. https://doi.org/10.1186/s13023-017-0675-4
Grant, N. (2021). Evaluating strategies to manage and endure challenging behavior in mucopolysaccharidoses. Orphanet Journal of Rare Diseases, 16, 1–5. https://doi.org/10.1186/s13023-021-01767-8
Heron, B., Mikaeloff, Y., Froissart, R., Caridade, G., Maire, I., Caillaud, C., & Tardieu, M. (2010). Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. American Journal of Medical Genetics Part A, 155(1), 58–68. https://doi.org/10.1002/ajmg.a.33779
Hoffman, F., Hoffman, S., Kunzmann, K., & Reis, M. (2020). Challenging behavior in mucopolysaccharidoses types 1-III and day-today coping strategies: A cross sectional explorative study. Orphanet Journal of Rare Diseases, 15, 275. https://doi.org/10.1186/s13023-020-01548-9
Mahon, L. V., Lomax, M., Grant, S., Cross, E., Hare, D. J., Wraith, J. E., & Canal, M. (2014). Assessment of sleep in children with mucopolysaccharidosis type III. PloS One, 9(2), e84128. https://doi.org/10.1371/journal.pone.0084128
Malcolm, C., Hain, R., Gibson, F., Adams, S., Anderson, G., & Forbat, L. (2012). Challenging symptoms in children with rare life-limiting conditions: Findings from a prospective diary and interview study with families. Acta Paediatrica, 101, 985–992. https://doi.org/10.1111/j.1651-2227.2012.026780.x
Malm, G., & Mansson, J. E. (2010). Mucopolysaccharidosis type III (Sanfilippo disease) in Sweden: Clinical presentation of 22 children diagnosed during a 30-year period. Acta Paediatrica, 99(8), 1253–1257. https://doi.org/10.1111/j.1651-2227.2010.01800.x
Mariotti, P., Marca, G. D., Iuvone, L., Vernacotola, S., Ricci, R., Mennuni, G. F., & Mazza, S. (2003). Sleep disorders in Sanfilippo syndrome: A polygraphic study. Clinical Electroencephalography, 34(1), 18–22. https://doi.org/10.1177/155005940303400108
Matson, J. L., Belva, B., Hattier, M. A., & Matson, M. L. (2011). Pica in persons with developmental disabilities: Characteristics, diagnosis, and assessment. Research in Autism Spectrum Disorders, 5(4), 1459–1464. https://doi.org/10.1016/j.rasd.2011.02.006
Meyer, A., Kossow, K., Gal, A., Muhlhausen, C., Braulke, T., & Muschol, N. (2007). Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A). Pediatrics, 120, 1255–1261. https://doi.org/10.1542/peds.2007-0282
Milnes, S. M., & Piazza, C. C. (2013). Intensive treatment of pediatric feeding disorders. In D. Reed, F. DiGennaro Reed, & J. Luiselli (Eds.), Handbook of crisis intervention and developmental disabilities. Issues in Clinical Child Psychology (pp. 393–408). Springer
Moss, J., & Howlin, P. (2009). Autism spectrum disorders in genetic syndromes: Implications for diagnosis, intervention and understanding the wider autism spectrum disorder population. Journal of Intellectual Disability Research, 53, 852–873. https://doi.org/10.1111/j.1365-2788.2009.01197.x
Napolitano, D. A., Jack, S. L., Sheldon, J. B., Williams, D. C., McAdam, D. B., & Schroeder, S. R. (1999). Drug-behavior interactions in persons with mental retardation and developmental disabilities. Mental Retardation and Developmental Disabilities Research Reviews, 5, 322–334. https://doi.org/10.1002/(SICI)1098-2779(1999)5:4%3c322::AID-MRDD10%3e3.3.CO;2-6
National Autism Center. (2009). The National Autism Center’s national standards report. Randolph, MA: National Autism Center
National Autism Center. (2015). The National Autism Center’s national standards report: Findings and conclusions, phase 2. Randolph, MA: National Autism Center.
Nidiffer, F. D., & Kelly, T. E. (1983). Developmental and degenerative patterns associated with cognitive, behavioral and motor difficulties in the Sanfilippo syndrome: An epidemiological study. Journal of Mental Deficiency Research, 27, 185–203. https://doi.org/10.1111/j.1365-2788.1983.tb00291.x
Ozonoff, S., Williams, B. J., & Landa, R. (2005). Parental report of the early development of children with regressive autism: The delays-plus-regression phenotype. Autism, 9, 461–486. https://doi.org/10.1177/136236105057880
Porter, K. A., O’Neill, C., Drake, E., Parker, S., Escolar, M. L., Montgomery, S., Moon, W., Worrall, C., & Peay, H. L. (2020). Parent experiences of Sanfilippo syndrome impact and unmet treatment needs: A qualitative assessment. Neural Therapy Online. https://doi.org/10.1007/s40120-0200-00226-z
Rumsey, R. K., Rudser, K., Delaney, K., Potegal, M., Whitley, C. B., & Shapiro, E. (2014). Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA. The Journal of Pediatrics, 164(5), 1147-1151. https://doi.org/10.1016/j.jpeds.2014.01.007
Schreck, K. A., Helsel, C., Paxon, A., Weston, K., & Daniels, M. (2018). Regression trends & treatment effectiveness to improve quality of life for a pre-adolescent girl with MPS IIIA. Journal of Developmental Disabilities, 30, 545–558. https://doi.org/10.1007/s10882.018.9601.5
Shapiro, E., Ahmend, A., Whiteley, C., & Delaney, K. (2018). Observing the advanced disease course in mucopolysaccharidosis, type IIIA; a case series. Molecular Genetics and Metabolism, 123(2), 123–126. https://doi.org/10.1016/j.ymgme.2017.11.014
Shapiro, E. G., & Eisengart, J. B. (2021). The natural history of neurocognition in MPS disorders: A review. Molecular Genetics and Metabolism, 133, 8–34. https://doi.org/10.1016/j.ymgme.2021.03.002
Shapiro, E. G., Nestrasil, I., Ahmed, A., Wey, A., Rudser, K. R., Haslett, P. A., & Potegal, M. (2015). Quantifying behaviors of children with Sanfilippo syndrome: The Sanfilippo behavior rating scale. Molecular genetics and metabolism, 114(4), 594–598. https://doi.org/10.1016/j.ymgme.2015.02.008
Shapiro, E. G., Nestrasil, I., Delaney, K. A., Rudser, K., Kovac, V., Nair, N., & Whitley, C. B. (2016). A prospective natural history study of mucopolysaccharidosis type IIIA. The Journal of Pediatrics, 170, 278–287. https://doi.org/10.1016/j.peds.2015.11.079
Sorrentino, N. C., & Fraldi, A. (2016). Brain targeting in MPS-IIIA. Pediatric Endocrinology Reviews, 13(Suppl 1), 630–638.
Sprague, R. L., & Werry, J. S. (1971). Methodology of psychopharmacological studies with the retarded. In N. R. Ellis (Ed.). International Review of Research in Mental Retardation (Vol 5, pp. 147–219). Academic Press
Stapleton, M., Hoshina, H., Sawamoto, K., Kubaski, F., Mason, R. W., Mackenzie, W. G., & Tomatsu, S. (2019). Critical review of current MPS guidelines and management. Molecular Genetics and Metabolism, 126(3), 238–245. https://doi.org/10.1016/j.ymgme.2018.07.001
Truxal, K. V., Fu, H., McCarty, D. M., McNally, K. A., Kunkler, K. L., Zumberge, N. A., Martin, L., Aylward, S. C., Alfano, L. N., Berry, K. M., Lowes, L. P., Corridore, M., McKee, C., McBride, K. L., & Flanigan, K. M. (2016). A prospective one-year natural history study of mucopolysaccharidosis types IIIA and IIIB: Implications for clinical trial design. Molecular Genetics and Metabolism, 119, 239–248. https://doi.org/10.1016/j.ymgme.2016.08.002
Valstar, M. J., Marchal, J. P., Grootenhuis, M., Colland, V., & Wijburg, F. A. (2011). Cognitive development in patients with mucopolysaccharidosis type III (Sanfilippo syndrome). Journal of Rare Diseases, 6, 43-43. https://doi.org/10.1186/1750-1172-6-43
Valstar, M. J., Neijs, S., Bruggenwirth, H. T., Olmer, R., Ruitjer, G. J., Wevers, R. A., & Wijburg, F. A. (2010). Mucopolysaccharidosis type IIIA: Clinical spectrum and genotype-phenotype correlations. Annals of Neurology, 68(6), 876–887. https://doi.org/10.1002/ana.22092
Valstar, M. J., Ruijter, J. G., van Diggelen, O. P., Poorthius, B. J., & Wijburg, F. A. (2008). Sanfilippo syndrome: A mini-review. Journal of Inheritable Metabolic Diseases, 31, 240–252. https://doi.org/10.1007/s10545-008-0838-5
van De Kamp, J. J., Niermeijer, M. F., Von Figura, K., & Giesberts, M. A. (1981). Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C). Clinical Genetics, 20, 152–160. https://doi.org/10.1111/j.1399-0004.1981.tb01821.x
Wijburg, F. A., Wegrzyn, G., Burton, B. K., & Tylki-Szymanska, A. (2013). Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta Paediatrica, 102, 462–470. https://doi.org/10.1111/apa.12169
Williams, D. E., & McAdam, D. (2012). Assessment, behavioral treatment, and prevention of pica: Clinical guidelines and recommendations for practitioners. Research in Developmental Disabilities, 33(6), 2050–2057. https://doi.org/10.1016/j.ridd.2012.04.001
Wolfenden, C., Wittkowski, A., & Hare, D. J. (2017). Symptoms of autism spectrum disorder (ASD) in individuals with mucopolysaccharide disease type III (Sanfilippo syndrome): A systematic review. Journal of Autism and Developmental Disorders, 47, 3620–3633. https://doi.org/10.1007/s10803-017-3262-6
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Research Ethics and Consent
N/A.
Employment
Kimberly A. Schreck was and remains a faculty member at the Penn State Harrisburg. Lindsay Kluth was a graduate student at time of paper completion and is currently employed with the Merakey Autism School.
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Schreck, K.A., Knapp, L.M. MPS-IIIA or Autism Spectrum Disorder?: Discrimination and Treatment. Rev J Autism Dev Disord 10, 383–390 (2023). https://doi.org/10.1007/s40489-021-00298-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40489-021-00298-z