Challenging behavior in mucopolysaccharidoses types I-III and day-to-day coping strategies: a cross sectional explorative study

Frederik Hoffmann, Susanne Hoffmann, Kevin Kunzmann, Markus Ries, Frederik Hoffmann, Susanne Hoffmann, Kevin Kunzmann, Markus Ries

Abstract

Background: Challenging behavior represents a core symptom in neuropathological mucopolysaccharidoses (MPS) and puts major strain on affected families. Although multimodal approaches including behavioral strategies to treatment could be valuable, there is lack of research to the effectiveness of specific measures. This explorative, cross-sectional study is aimed at the collection of parental experiences regarding effective day-to-day measures against challenging behavior in MPS and focuses on 4 major research questions: First: What is challenging behavior in MPS? Second: Which strategies are helpful in the day-to-day coping with challenging behavior? Third: How strong is parental acceptance of illness and the disorder's impact on family relationships? Fourth: What are beneficial personal and interfamilial strategies for generally coping with the disorder?

Methods: A semi structured questionnaire was designed de novo in cooperation with affected families. 37/268 questionnaires were returned (rate: 13.8%), of which 34 (MPS I: n = 8, MPS II: n = 8; MPS III: n = 18) could be included in data analysis in accordance with inclusion criteria. Assessment of challenging symptoms was based on perceived frequency, parent- and child stress. Exploration of possible coping strategies for challenging behavior and general illness-related strain included the evaluation of perceived effectiveness. Questionnaires were completed by patient's relatives and analyzed for strategies to cope with challenging behavior and the disorder's impact. STROBE criteria were respected.

Results: MPS I was reported to show lower frequency and better perceived manageability of challenging behavior than MPS II and -III. Sleep disturbance, hyperactivity, agitation, aggression and orality seemed relevant symptoms regarding frequency and/or parent stress. Reported measures were manifold, worthwhile approaches against challenging behavior appeared to be aiming at distraction, relief and environmental changes. Medication and non-medication approaches were rated similarly effective. Social exchange, private space and networking with other affected families seemed highly important for personal and interfamilial well-being.

Conclusions: Multimodal mentoring for affected families could be based on the following equivalent pillars: (1) Medication therapy for challenging behavior including evaluation of cost and benefit (2) Guided implementation and re-evaluation of specific behavioral measures against challenging behavior. (3) Psychosocial support of MPS-families, including options for strengthening parental well-being and family functioning. Trial registration This study was registered at clinicaltrials.gov prior to study start (NCT-Number: NCT03161171, Date: 2017/05/19).

Keywords: Challenging behavior; Coping; Day-to-day coping; Hunter; Hurler; MPS; Mucopolysaccharidoses; Sanfilippo.

Conflict of interest statement

The authors declare no potential conflicts of interest with respect to research, authorship and/or publication of this article.

Figures

Fig. 1
Fig. 1
MPS I-III: symptom frequency; respective stress if symptom is present. Symptom frequency in  % of all questionnaires (n = 34); respective stress levels if symptom is existent (at least with moderate frequency) as reported on VAS with range 0.00 (low) to 5.00 (high)

References

    1. Baehner F, Schmiedeskamp C, Krummenauer F, Miebach E, Bajbouj M, Whybra C, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis. 2005 doi: 10.1007/s10545-005-0112-z.
    1. Neufeld EF, Muenzer J. The Mucopolysaccharidoses. Online Metab Mol Bases Inherit Dis. 2001 doi: 10.1036/ommbid.165.
    1. Zielonka M, Garbade SF, Kolker S, Hoffmann GF, Ries M. Quantitative clinical characteristics of 53 patients with MPS VII: a cross-sectional analysis. Genet Med. 2017 doi: 10.1038/gim.2017.10.
    1. Muenzer J, Wraith JE, Clarke LA, International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009; 10.1542/peds.2008-0416.
    1. Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr. 2004 doi: 10.1016/j.jpeds.2004.01.052.
    1. Schwartz IV, Ribeiro MG, Mota JG, Toralles MB, Correia P, Horovitz D, et al. A clinical study of 77 patients with mucopolysaccharidosis type II. Acta Paediatr. 2007 doi: 10.1111/j.1651-2227.2007.00212.x.
    1. Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA. Sanfilippo syndrome: a mini-review. J Inherit Metab Dis. 2008 doi: 10.1007/s10545-008-0838-5.
    1. Cleary MA, Wraith JE. Management of mucopolysaccharidosis type III. Arch Dis Child. 1993 doi: 10.1136/adc.69.3.403.
    1. Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, et al. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 doi: 10.1007/s00431-007-0635-4.
    1. Moore D, Connock MJ, Wraith E, Lavery C. The prevalence of and survival in Mucopolysaccharidosis I: hurler, Hurler-Scheie and Scheie syndromes in the UK. Orphanet J Rare Dis. 2008 doi: 10.1186/1750-1172-3-24.
    1. Beck M, Arn P, Giugliani R, Muenzer J, Okuyama T, Taylor J, et al. The natural history of MPS I: global perspectives from the MPS I Registry. Genet Med. 2014 doi: 10.1038/gim.2014.25.
    1. Buhrman D, Thakkar K, Poe M, Escolar ML. Natural history of Sanfilippo syndrome type A. J Inherit Metab Dis. 2014 doi: 10.1007/s10545-013-9661-8.
    1. Malcolm C, Adams S, Anderson G, Gibson F, Hain R, Morley A, et al. The symptom profile and experience of children with rare life-limiting conditions: Perspectives of their families and key health professionals. In: Faculty of Health Sciences and Sport Research Reports. University of Stirling CCRC. 2011. . Accessed 10 Okt 2019.
    1. Bax MC, Colville GA. Behaviour in mucopolysaccharide disorders. Arch Dis Child. 1995 doi: 10.1136/adc.73.1.77.
    1. Escolar ML, Jones SA, Shapiro EG, Horovitz DDG, Lampe C, Amartino H. Practical management of behavioral problems in mucopolysaccharidoses disorders. Mol Genet Metab. 2017 doi: 10.1016/j.ymgme.2017.09.010.
    1. Cross EM, Hare DJ. Behavioural phenotypes of the mucopolysaccharide disorders: a systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders. J Inherit Metab Dis. 2013 doi: 10.1007/s10545-012-9572-0.
    1. Leighton SE, Papsin B, Vellodi A, Dinwiddie R, Lane R. Disordered breathing during sleep in patients with mucopolysaccharidoses. Int J Pediatr Otorhinolaryngol. 2001 doi: 10.1016/s0165-5876(01)00417-7.
    1. Guerrero JM, Pozo D, Diaz-Rodriguez JL, Martinez-Cruz F, Vela-Campos F. Impairment of the melatonin rhythm in children with Sanfilippo syndrome. J Pineal Res. 2006 doi: 10.1111/j.1600-079X.2005.00294.x.
    1. Fraser J, Wraith JE, Delatycki MB. Sleep disturbance in mucopolysaccharidosis type III (Sanfilippo syndrome): a survey of managing clinicians. Clin Genet. 2002 doi: 10.1034/j.1399-0004.2002.620512.x.
    1. Fraser J, Gason AA, Wraith JE, Delatycki MB. Sleep disturbance in Sanfilippo syndrome: a parental questionnaire study. Arch Dis Child. 2005 doi: 10.1136/adc.2004.065482.
    1. Kalkan Ucar S, Ozbaran B, Demiral N, Yuncu Z, Erermis S, Coker M. Clinical overview of children with mucopolysaccharidosis type III A and effect of Risperidone treatment on children and their mothers psychological status. Brain Dev. 2010 doi: 10.1016/j.braindev.2008.12.010.
    1. Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J, et al. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics. 2009 doi: 10.1542/peds.2007-3847.
    1. Muenzer J, Beck M, Eng CM, Giugliani R, Harmatz P, Martin R, et al. Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome. Genet Med. 2011 doi: 10.1097/GIM.0b013e3181fea459.
    1. Begley DJ, Pontikis CC, Scarpa M. Lysosomal storage diseases and the blood-brain barrier. Curr Pharm Des. 2008 doi: 10.2174/138161208784705504.
    1. Scarpa M, Orchard PJ, Schulz A, Dickson PI, Haskins ME, Escolar ML, et al. Treatment of brain disease in the mucopolysaccharidoses. Mol Genet Metab. 2017 doi: 10.1016/j.ymgme.2017.10.007.
    1. Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, et al. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J Med. 2018 doi: 10.1056/NEJMoa1712649.
    1. Barone R, Pellico A, Pittala A, Gasperini S. Neurobehavioral phenotypes of neuronopathic mucopolysaccharidoses. Ital J Pediatr. 2018 doi: 10.1186/s13052-018-0561-2.
    1. Garbade SF, Zielonka M, Mechler K, Kolker S, Hoffmann GF, Staufner C, et al. FDA orphan drug designations for lysosomal storage disorders: a cross-sectional analysis. PLoS ONE. 2020 doi: 10.1371/journal.pone.0230898.
    1. Meadows AS, Duncan FJ, Camboni M, Waligura K, Montgomery C, Zaraspe K, et al. A GLP-compliant toxicology and biodistribution study: systemic delivery of an rAAV9 vector for the treatment of mucopolysaccharidosis IIIB. Hum Gene Ther Clin Dev. 2015 doi: 10.1089/humc.2015.132.
    1. Ou L, DeKelver RC, Rohde M, Tom S, Radeke R, St Martin SJ, et al. ZFN-mediated in vivo genome editing corrects murine hurler syndrome. Mol Ther. 2019 doi: 10.1016/j.ymthe.2018.10.018.
    1. Laoharawee K, DeKelver RC, Podetz-Pedersen KM, Rohde M, Sproul S, Nguyen HO, et al. Dose-dependent prevention of metabolic and neurologic disease in murine MPS II by ZFN-mediated in vivo genome editing. Mol Ther. 2018 doi: 10.1016/j.ymthe.2018.03.002.
    1. Ferla R, Claudiani P, Savarese M, Kozarsky K, Parini R, Scarpa M, et al. Prevalence of anti-adeno-associated virus serotype 8 neutralizing antibodies and arylsulfatase B cross-reactive immunologic material in mucopolysaccharidosis VI patient candidates for a gene therapy trial. Hum Gene Ther. 2015 doi: 10.1089/hum.2014.109.
    1. Somanadhan S, Larkin PJ. Parents’ experiences of living with, and caring for children, adolescents and young adults with Mucopolysaccharidosis (MPS) Orphanet J Rare Dis. 2016 doi: 10.1186/s13023-016-0521-0.
    1. Grant S, Cross E, Wraith JE, Jones S, Mahon L, Lomax M, et al. 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) J Inherit Metab Dis. 2013 doi: 10.1007/s10545-012-9558-y.
    1. Roberts J, Stewart C, Kearney S. Management of the behavioural manifestations of Hunter syndrome. Br J Nurs. 2016 doi: 10.12968/bjon.2016.25.1.22.
    1. Armstrong RA. When to use the Bonferroni correction. Ophthalmic Physiol Opt. 2014 doi: 10.1111/opo.12131.
    1. Perneger TV. What’s wrong with Bonferroni adjustments. Br Med J. 1998 doi: 10.1136/bmj.316.7139.1236.
    1. Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology. 1990;1(1):43–46. doi: 10.1097/00001648-199001000-00010.
    1. Nidiffer FD, Kelly TE. Developmental and degenerative patterns associated with cognitive, behavioural and motor difficulties in the Sanfilippo syndrome: an epidemiological study. J Ment Defic Res. 1983 doi: 10.1111/j.1365-2788.1983.tb00291.x.
    1. Collins JJ, Devine TD, Dick GS, Johnson EA, Kilham HA, Pinkerton CR, et al. The measurement of symptoms in young children with cancer: the validation of the Memorial Symptom Assessment Scale in children aged 7-12. J Pain Symptom Manage. 2002 doi: 10.1016/s0885-3924(01)00375-x.
    1. Colville GA, Watters JP, Yule W, Bax M. Sleep problems in children with Sanfilippo syndrome. Dev Med Child Neurol. 1996 doi: 10.1111/j.1469-8749.1996.tb12114.x.
    1. Holt J, Poe MD, Escolar ML. Early clinical markers of central nervous system involvement in mucopolysaccharidosis type II. J Pediatr. 2011 doi: 10.1016/j.jpeds.2011.03.019.
    1. Canal MM, Wilkinson FL, Cooper JD, Wraith JE, Wynn R, Bigger BW. Circadian rhythm and suprachiasmatic nucleus alterations in the mouse model of mucopolysaccharidosis IIIB. Behav Brain Res. 2010 doi: 10.1016/j.bbr.2010.01.045.
    1. Jan JE, O’Donnell ME. Use of melatonin in the treatment of paediatric sleep disorders. J Pineal Res. 1996 doi: 10.1111/j.1600-079x.1996.tb00286.x.
    1. Young ID, Harper PS. The natural history of the severe form of Hunter’s syndrome: a study based on 52 cases. Dev Med Child Neurol. 1983 doi: 10.1111/j.1469-8749.1983.tb13794.x.
    1. Shapiro EG, Nestrasil I, Ahmed A, Wey A, Rudser KR, Delaney KA, et al. Quantifying behaviors of children with Sanfilippo syndrome: the Sanfilippo Behavior Rating Scale. Mol Genet Metab. 2015 doi: 10.1016/j.ymgme.2015.02.008.
    1. Turner M. Annotation: repetitive behaviour in autism: a review of psychological research. J Child Psychol Psychiatry. 1999 doi: 10.1111/1469-7610.00502.
    1. Deshpande S, Sathe K. A child with advanced mucopolysaccharidosis presenting with severe behavioural problems. ASEAN J Psychiatry. 2015;16(1):127–130.
    1. Verhoeven WM, Csepan R, Marcelis CL, Lefeber DJ, Egger JI, Tuinier S. Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia. Acta Psychiatr Scand. 2010 doi: 10.1111/j.1600-0447.2009.01521.x.
    1. Rumsey RK, Rudser K, Delaney K, Potegal M, Whitley CB, Shapiro E. Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA. J Pediatr. 2014 doi: 10.1016/j.jpeds.2014.01.007.
    1. Shapiro E, King K, Ahmed A, Rudser K, Rumsey R, Yund B, et al. The neurobehavioral phenotype in mucopolysaccharidosis type IIIB: an exploratory study. Mol Genet Metab Rep. 2016 doi: 10.1016/j.ymgmr.2016.01.003.
    1. Holt JB, Poe MD, Escolar ML. Natural progression of neurological disease in mucopolysaccharidosis type II. Pediatrics. 2011 doi: 10.1542/peds.2010-1274.
    1. Kandel I, Merrick J. The child with a disability: parental acceptance, management and coping. Sci World J. 2007 doi: 10.1100/tsw.2007.265.
    1. Raina P, O’Donnell M, Rosenbaum P, Brehaut J, Walter SD, Russell D, et al. The health and well-being of caregivers of children with cerebral palsy. Pediatrics. 2005 doi: 10.1542/peds.2004-1689.
    1. Scharpen AL, Stille CJ. From strangers in a foreign land to active, engaged citizens. Pediatrics. 2018 doi: 10.1542/peds.2017-1845.
    1. Enders CK. Applied missing data analysis. New York: Guilford Press; 2010.
    1. Newman DA. Missing data: five practical guidelines. Organ Res Methods. 2014 doi: 10.1177/1094428114548590.
    1. Enders CK. Multiple imputation as a flexible tool for missing data handling in clinical research. Behav Res Ther. 2017 doi: 10.1016/j.brat.2016.11.008.
    1. Wolfenden C, Wittkowski A, Hare DJ. Symptoms of autism spectrum disorder (ASD) in individuals with mucopolysaccharide disease type III (sanfilippo syndrome): a systematic review. J Autism Dev Disord. 2017 doi: 10.1007/s10803-017-3262-6.
    1. Sanders M, Mazzucchelli T, Studman L. Stepping Stones Triple P: The theoretical basis and development of an evidence-based positive parenting program for families with a child who has a disability. J Intellect Dev Disabil. 2004 doi: 10.1080/13668250412331285127.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner