Neurocognitive Functioning of Pediatric and Young Adult Patients with Gaucher Disease, Type 1
Main Article Content
Abstract
This exploratory study aimed to evaluate the cognitive and executive functioning of sixteen pediatric and fifteen young adult (ages 5 through 30) patients with Gaucher disease, Type 1. The neurocognitive functioning of children with Gaucher disease, Type 1 was based on self- and parent-proxy reports while neurocognitive functioning in young adults was based on self-report only. Results showed that pediatric participants with Gaucher disease, Type 1 on self-report demonstrated a trend toward weaker cognitive functioning than healthy children. Parent proxy-reports did not show significantly different cognitive functioning of children with Gaucher disease, Type 1 compared to healthy peers. Young adults with Gaucher disease, Type 1 self-reported no significant differences in cognitive functioning from healthy young adults. No group differences in executive functioning were observed for child or young adult samples. Parent-reported disease severity was not associated with cognitive outcomes among the pediatric or young adult samples. Results suggest possible mild cognitive weaknesses among children with Gaucher disease, Type 1 while cognition in young adults appears relatively well preserved. This is the first independent examination of cognitive functioning among children and young adults with GD1. Additional studies in younger patients with Gaucher disease, Type 1 are needed to identify possible cognitive dysfunction and elucidate underlying mechanisms.
Keywords:
Gaucher disease, pediatric, neurocognitive functioning, inborn error of metabolism
Article Details
How to Cite
ALIOTO, Andrea G. et al.
Neurocognitive Functioning of Pediatric and Young Adult Patients with Gaucher Disease, Type 1.
Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3028>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v10i9.3028.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Stirnemann J, Belmatoug N, Camou F, et al. A review of Gaucher disease pathophysiology, clinical presentation and treatments. Int. J. Mol. Sci., 2017;18(441),1-30. doi:10.3390/ijms18020441
2. Charrow J, Andersson HC, Kaplan P, et al. The Gaucher registry: Demographics and disease characteristics of 1698 patients with Gaucher disease. Arch. Intern. Med. 2000;160(18),2835-2843. doi:10.1001/archinte.160.18.2835
3. Rosenbloom, BE, Weinreb NJ. Gaucher disease: a comprehensive review. Crit. Rev. Oncog., 2013;18(3),163-75. doi:10.1615/critrevoncog.2013006060
4. Kaplan P, Baris H, De Meirleir L, et al. Revised recommendations for the management of Gaucher disease in children. European J. Pediatr. 2013;172,447-458. doi:10.1007/s00431-012-1771-z
5. Capabolo JL, Saenz de Cabezón A, Fraile J, et al. Neurological evaluation of patients with Gaucher disease diagnosed as type 1. J Neurol. Neurosurg. Psychiatry. 2008;79(2),219-222. doi:10.1136/jnnp.2006.111518
6. Roshan Lal, T, Sidransky, E. The Spectrum of Neurological Manifestations Associated with Gaucher Disease. Diseases, 2017;5(1),10. doi:10.3390/diseases5010010
7. Biegstraaten M, Mengel E, Maródi L, et al. Peripheral neuropathy in adult type 1 Gaucher disease: A 2-year prospective observational study. Brain. 2010;133(10),2909-2919. doi:1093/brain/awq198
8. Biegstraaten M, van Schaik IN, Aerts JMFG, Hollak, CEM. ‘Non-neuronopathic’ Gaucher disease reconsidered. Prevalence of neurological manifestations in a Dutch cohort of type I Gaucher disease patients and a systematic review of the literature. J. Inherit. Metab. Dis. 2008; 31(3),337-349. doi:10.1007/s10545-008-0832-y
9. Chérin P, Rose C, de Roux-Serratrice C, et al. The neurological manifestations of Gaucher disease type 1: the French Observatoire on Gaucher disease (FROG). J. Inherit. Metab. Dis. 2010;33(4),331-338. doi:10.1007/s10545-010-9095-5
10. Aflaki E, Westbroek W, Sidransky E. The complicated relationship between Gaucher disease and parkinsonism: Insights from a rare disease. Neuron. 2017;93(4),737-746. doi:10.1016/j.neuron.2017.01.018
11. Davies EH, Seunarine KK, Banks T, Clark CA, Vellodi A. Brain white matter abnormalities in paediatric Gaucher Type I and Type III using diffusion tensor imaging. Image in Metab. Med. 2011;34(2),549-555. doi:10.1007/s10545-011-9288-6
12. Kang H, Zhang M, Ouyang M, et al. Brain white matter microstructural alterations in children of type I Gaucher disease characterized with diffusion tensor MR imaging. Eur. J. Radiol. 2018;102, 22-29. doi:10.1016/j.ejrad.2018.02.014
13. Zhang M, Wang S, Hu D, et al. Altered brain functional network in children with type 1 Gaucher disease: A longitudinal graph theory-based study. Neuroradiology. 2019;61,63-70. doi:10.1007/s00234-018-2104-3
14. Kartha RV, Joers J, Terluk MR, et al. Neurochemical abnormalities in patients with type 1 Gaucher disease on standard of care therapy. J. Inherit. Metab. Dis. 2020;43(3),564-573. doi:10.1002/jimd.12182
15. Pastores G M, Barnett NL, Bathan P, Kolodny EH A neurological symptom survey of patients with type I Gaucher disease. J. Inherit. Metab. Dis. 2003;26,641-645. doi:10.1023/B:BOLI.0000005623.60471.51
16. Elstein D, Guedalia J, Doniger GM, et al. Computerized cognitive testing in patients with type I Gaucher disease: Effects of enzyme replacement therapy. Genet. in Med, 2005;7(2),124-130. doi:0.1097/01.GIM.0000153666.23707.BA
17. Biegstraaten M, Wesnes KA, Luzy, C, et al. The cognitive profile of type 1 Gaucher disease patients. J. Inherit. Metab. Dis., 2012;35,1093-1099. doi:10.1007/s10545-012-9460-7
18. Lopez G, Kim J, Wiggs E, et al. Clinical course and prognosis in patients with Gaucher disease and parkinsonism. Neurol. Genet, 2016;2(2),e57. doi:10.1212/NXG.0000000000000057
19. Li Y, Li P, Liang H, Zhao Z, Hashimoto M, Wei H. Gaucher-associated parkinsonism. Cell. Mol. Neurobiol. 2015;35,755-761.
doi:10.1007/s10571-015-0176-8
20. Steward AM, Wiggs E, Lindstrom T, et al. Variation in cognitive function over time in Gaucher disease type 3. Neurology. 2019;93(24),e2772-e2283. doi:10.1212/WNL.0000000000008618
21. Tantawy AA, Sherif EM, Adly AA, Hassanine S, Awad AH Evoked potentials and neurocognitive functions in pediatric Egyptian Gaucher patients on enzyme replacement therapy: A single center experience. J. Inherit. Metab. Dis. 2013;36(6),1025-1037. doi:10.1007/s10545-013-9597-z
22. Varni JW, Burwinkle TM, Katz ER, Meeske K, Dickinson P. The PedsQL in pediatric cancer: Reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module. Cancer, 2002;94(7),2090-2106. doi:10.1002/cncr.10428
23. Varni JW, Limbers CA. The PedsQL Multidimensional Fatigue Scale in young adults: Feasibility, reliability and validity in a university student population. Qual. Life Res. 2008;17(1),105-114. doi:10.1007/s11136-007-9282-5
24. Varni JW, Limbers CA, Sorensen LG, Neighbors K, Martz K, Bucuvalas JC, Alonso, EM. PedsQL Cognitive Functioning Scale in Pediatric Liver Transplant Recipients: Feasibility, reliability and validity. Qual. Life Res., 2011;20(6),913-921. doi:10.1007/s11136-010-9823-1
25. McCarthy ML, Mackenzie E, Durbin D, & Aitken M. The Pediatric Quality of Life Inventory: An Evaluation of its Reliability and Validity for Children with Traumatic Brain Injury. Arch. Phys. Med. and Rehabil. 2005;86(10),1901-1909. doi:10.1016/j.apmr.2005.03.026
26. Swanson JO, Vavilala MS, Wang J, et al. Association of initial CT findings with quality-of-life outcomes for traumatic brain injury in children. Ped. Radio., 2012;42,974-981. doi:10.1007/s00247-012-2372-8
27. Gioia GA, Isquith PK, Guy SC, Kenworthy L. Behavior Rating Inventory of Executive Function. PAR;2000
28. Roth RM, Isquith PK, Gioia, GA. Assessment of Executive functioning using the Behavior Rating Inventory of Executive Function (BRIEF). In S. Goldstein & J. A. Naglieri (Eds.), Handbook of Executive Functioning. Springer; 2005.
29. Siegel S, Castellan NJ. Nonparametric statistics for the behavioral sciences. 2nd ed. New York: Mcgraw-Hill Book Company; 1988.
30. Eiser C, Morse R. A review of measures of quality of life for children with chronic illness. Arch. Dis. Child 2001;84(3),205-211. doi:10.1136/adc.84.3.205.
31. Compas BE, Jaser SS, Reeslund K, et al. Neurocognitive deficits in children with chronic health conditions. Am Psychol. 2017;72(4),326-338. doi:10.1037/amp0000042
32. Schuman WB, La Greca AM. Social correlates of chronic illness. In: Brown R T (Ed.). Cognitive aspects of chronic illness in children. New York: Guilford; 1999.
33. Compas BE, Jaser SS, Dunn MJ, et al. Coping with chronic illness in childhood and adolescence. Annu. Rev. Clin. Psychol. 2012;8,455-480. doi:10.1146/annurev-clinpsy-032511-143108
34. Fairley C, Zimran A, Phillips M, et al. Phenotypic heterogeneity of N370S homozygotes with type I Gaucher disease: An analysis of 798 patients from the ICGG Gaucher Registry. J. Inherit. Metab. Dis. 2008;31(6),798-744. doi:10.1007/s10545-008-0868-z
35. Grabowski G, Kolodny EH, Weinreb N. Gaucher disease: Phenotypic and genetic variation. In Scriver CR, Beaudet AL, Valle D, et al., eds. The online metabolic and molecular basis of inherited metabolic disease. New York: McGraw-Hill; 2006.
36. Carthy T, Horesh N, Apter A, Edge MD, & Gross, JJ. Emotional reactivity and cognitive regulation in anxious children. Behav. Res.Ther. 2010.48(5),384-393. doi:10.1016/j.brat.2009.12.013
37. Wagner S, Müller C, Helmreich I, Huss M, Tadić A. A meta-analysis of cognitive functions in children and adolescents with major depressive disorder. Eur. Child Adolesc. Psychiatry. 2015;24,5-19, doi:10.1007/s00787-014-0559-2
38. Alioto AG, Gomez R. Moses J, Paternostro J, Packman S, Packman W. Quality of life and psychological functioning in pediatric and young adult patients with Gaucher disease, type 1. Am. J. Med. Genet. Part A, 2020;182A,1130-1142. doi:10.1002/ajmg.a.61533
39. Weinreb N, Goldblatt J, Villalobos J, et al. Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment. J. Inherit. Metab. Dis., 2013;36(3),543-554. doi:10.1007/s10545-012-9528-4
2. Charrow J, Andersson HC, Kaplan P, et al. The Gaucher registry: Demographics and disease characteristics of 1698 patients with Gaucher disease. Arch. Intern. Med. 2000;160(18),2835-2843. doi:10.1001/archinte.160.18.2835
3. Rosenbloom, BE, Weinreb NJ. Gaucher disease: a comprehensive review. Crit. Rev. Oncog., 2013;18(3),163-75. doi:10.1615/critrevoncog.2013006060
4. Kaplan P, Baris H, De Meirleir L, et al. Revised recommendations for the management of Gaucher disease in children. European J. Pediatr. 2013;172,447-458. doi:10.1007/s00431-012-1771-z
5. Capabolo JL, Saenz de Cabezón A, Fraile J, et al. Neurological evaluation of patients with Gaucher disease diagnosed as type 1. J Neurol. Neurosurg. Psychiatry. 2008;79(2),219-222. doi:10.1136/jnnp.2006.111518
6. Roshan Lal, T, Sidransky, E. The Spectrum of Neurological Manifestations Associated with Gaucher Disease. Diseases, 2017;5(1),10. doi:10.3390/diseases5010010
7. Biegstraaten M, Mengel E, Maródi L, et al. Peripheral neuropathy in adult type 1 Gaucher disease: A 2-year prospective observational study. Brain. 2010;133(10),2909-2919. doi:1093/brain/awq198
8. Biegstraaten M, van Schaik IN, Aerts JMFG, Hollak, CEM. ‘Non-neuronopathic’ Gaucher disease reconsidered. Prevalence of neurological manifestations in a Dutch cohort of type I Gaucher disease patients and a systematic review of the literature. J. Inherit. Metab. Dis. 2008; 31(3),337-349. doi:10.1007/s10545-008-0832-y
9. Chérin P, Rose C, de Roux-Serratrice C, et al. The neurological manifestations of Gaucher disease type 1: the French Observatoire on Gaucher disease (FROG). J. Inherit. Metab. Dis. 2010;33(4),331-338. doi:10.1007/s10545-010-9095-5
10. Aflaki E, Westbroek W, Sidransky E. The complicated relationship between Gaucher disease and parkinsonism: Insights from a rare disease. Neuron. 2017;93(4),737-746. doi:10.1016/j.neuron.2017.01.018
11. Davies EH, Seunarine KK, Banks T, Clark CA, Vellodi A. Brain white matter abnormalities in paediatric Gaucher Type I and Type III using diffusion tensor imaging. Image in Metab. Med. 2011;34(2),549-555. doi:10.1007/s10545-011-9288-6
12. Kang H, Zhang M, Ouyang M, et al. Brain white matter microstructural alterations in children of type I Gaucher disease characterized with diffusion tensor MR imaging. Eur. J. Radiol. 2018;102, 22-29. doi:10.1016/j.ejrad.2018.02.014
13. Zhang M, Wang S, Hu D, et al. Altered brain functional network in children with type 1 Gaucher disease: A longitudinal graph theory-based study. Neuroradiology. 2019;61,63-70. doi:10.1007/s00234-018-2104-3
14. Kartha RV, Joers J, Terluk MR, et al. Neurochemical abnormalities in patients with type 1 Gaucher disease on standard of care therapy. J. Inherit. Metab. Dis. 2020;43(3),564-573. doi:10.1002/jimd.12182
15. Pastores G M, Barnett NL, Bathan P, Kolodny EH A neurological symptom survey of patients with type I Gaucher disease. J. Inherit. Metab. Dis. 2003;26,641-645. doi:10.1023/B:BOLI.0000005623.60471.51
16. Elstein D, Guedalia J, Doniger GM, et al. Computerized cognitive testing in patients with type I Gaucher disease: Effects of enzyme replacement therapy. Genet. in Med, 2005;7(2),124-130. doi:0.1097/01.GIM.0000153666.23707.BA
17. Biegstraaten M, Wesnes KA, Luzy, C, et al. The cognitive profile of type 1 Gaucher disease patients. J. Inherit. Metab. Dis., 2012;35,1093-1099. doi:10.1007/s10545-012-9460-7
18. Lopez G, Kim J, Wiggs E, et al. Clinical course and prognosis in patients with Gaucher disease and parkinsonism. Neurol. Genet, 2016;2(2),e57. doi:10.1212/NXG.0000000000000057
19. Li Y, Li P, Liang H, Zhao Z, Hashimoto M, Wei H. Gaucher-associated parkinsonism. Cell. Mol. Neurobiol. 2015;35,755-761.
doi:10.1007/s10571-015-0176-8
20. Steward AM, Wiggs E, Lindstrom T, et al. Variation in cognitive function over time in Gaucher disease type 3. Neurology. 2019;93(24),e2772-e2283. doi:10.1212/WNL.0000000000008618
21. Tantawy AA, Sherif EM, Adly AA, Hassanine S, Awad AH Evoked potentials and neurocognitive functions in pediatric Egyptian Gaucher patients on enzyme replacement therapy: A single center experience. J. Inherit. Metab. Dis. 2013;36(6),1025-1037. doi:10.1007/s10545-013-9597-z
22. Varni JW, Burwinkle TM, Katz ER, Meeske K, Dickinson P. The PedsQL in pediatric cancer: Reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module. Cancer, 2002;94(7),2090-2106. doi:10.1002/cncr.10428
23. Varni JW, Limbers CA. The PedsQL Multidimensional Fatigue Scale in young adults: Feasibility, reliability and validity in a university student population. Qual. Life Res. 2008;17(1),105-114. doi:10.1007/s11136-007-9282-5
24. Varni JW, Limbers CA, Sorensen LG, Neighbors K, Martz K, Bucuvalas JC, Alonso, EM. PedsQL Cognitive Functioning Scale in Pediatric Liver Transplant Recipients: Feasibility, reliability and validity. Qual. Life Res., 2011;20(6),913-921. doi:10.1007/s11136-010-9823-1
25. McCarthy ML, Mackenzie E, Durbin D, & Aitken M. The Pediatric Quality of Life Inventory: An Evaluation of its Reliability and Validity for Children with Traumatic Brain Injury. Arch. Phys. Med. and Rehabil. 2005;86(10),1901-1909. doi:10.1016/j.apmr.2005.03.026
26. Swanson JO, Vavilala MS, Wang J, et al. Association of initial CT findings with quality-of-life outcomes for traumatic brain injury in children. Ped. Radio., 2012;42,974-981. doi:10.1007/s00247-012-2372-8
27. Gioia GA, Isquith PK, Guy SC, Kenworthy L. Behavior Rating Inventory of Executive Function. PAR;2000
28. Roth RM, Isquith PK, Gioia, GA. Assessment of Executive functioning using the Behavior Rating Inventory of Executive Function (BRIEF). In S. Goldstein & J. A. Naglieri (Eds.), Handbook of Executive Functioning. Springer; 2005.
29. Siegel S, Castellan NJ. Nonparametric statistics for the behavioral sciences. 2nd ed. New York: Mcgraw-Hill Book Company; 1988.
30. Eiser C, Morse R. A review of measures of quality of life for children with chronic illness. Arch. Dis. Child 2001;84(3),205-211. doi:10.1136/adc.84.3.205.
31. Compas BE, Jaser SS, Reeslund K, et al. Neurocognitive deficits in children with chronic health conditions. Am Psychol. 2017;72(4),326-338. doi:10.1037/amp0000042
32. Schuman WB, La Greca AM. Social correlates of chronic illness. In: Brown R T (Ed.). Cognitive aspects of chronic illness in children. New York: Guilford; 1999.
33. Compas BE, Jaser SS, Dunn MJ, et al. Coping with chronic illness in childhood and adolescence. Annu. Rev. Clin. Psychol. 2012;8,455-480. doi:10.1146/annurev-clinpsy-032511-143108
34. Fairley C, Zimran A, Phillips M, et al. Phenotypic heterogeneity of N370S homozygotes with type I Gaucher disease: An analysis of 798 patients from the ICGG Gaucher Registry. J. Inherit. Metab. Dis. 2008;31(6),798-744. doi:10.1007/s10545-008-0868-z
35. Grabowski G, Kolodny EH, Weinreb N. Gaucher disease: Phenotypic and genetic variation. In Scriver CR, Beaudet AL, Valle D, et al., eds. The online metabolic and molecular basis of inherited metabolic disease. New York: McGraw-Hill; 2006.
36. Carthy T, Horesh N, Apter A, Edge MD, & Gross, JJ. Emotional reactivity and cognitive regulation in anxious children. Behav. Res.Ther. 2010.48(5),384-393. doi:10.1016/j.brat.2009.12.013
37. Wagner S, Müller C, Helmreich I, Huss M, Tadić A. A meta-analysis of cognitive functions in children and adolescents with major depressive disorder. Eur. Child Adolesc. Psychiatry. 2015;24,5-19, doi:10.1007/s00787-014-0559-2
38. Alioto AG, Gomez R. Moses J, Paternostro J, Packman S, Packman W. Quality of life and psychological functioning in pediatric and young adult patients with Gaucher disease, type 1. Am. J. Med. Genet. Part A, 2020;182A,1130-1142. doi:10.1002/ajmg.a.61533
39. Weinreb N, Goldblatt J, Villalobos J, et al. Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment. J. Inherit. Metab. Dis., 2013;36(3),543-554. doi:10.1007/s10545-012-9528-4